bluuebunny/crossref_metadata_2025 huggingface dataset:
The Clinical Viewpoint: Definitions, Limitations of RECIST, Practical Considerations of Measurement
Authors: Villaruz Liza C. , Socinski Mark A.
Published: May 2013

In selecting an endpoint in clinical trial design, it is important to consider that the endpoint is both reliably measured and clinically meaningful. As such, overall survival (OS) has traditionally been considered the most clinically relevant and convincing endpoint in clinical trial design as long as it is accompanied by preservation in quality of life. However, progression-free survival (PFS) is increasingly more prominent in clinical trial design because of feasibility issues (smaller sample sizes and shorter follow-up). PFS has the advantage of taking into account not only responsive disease, but stable disease as well, an issue of particular importance in the relapsed and refractory setting in which therapies are often associated with a minimal to nil response but may still confer a survival advantage. Finally, PFS has a significant advantage in molecularly selected populations, in whom OS advantages are difficult to detect due to the effects of crossover. With an understanding of the limitations and biases that are introduced with PFS as a primary endpoint, we believe that PFS is not only a viable but also a necessary alternative to OS in assessing the efficacy of selected novel-targeted therapies in molecularly defined cancer populations. Ultimately, the selection of a clinical trial endpoint should not be based on a one-size-fits all approach; rather, it should be based on the specifics of the therapeutic strategy being tested and the population under study. Clin Cancer Res; 19(10); 2629–36. ©2013 AACR.
The Imaging Viewpoint: How Imaging Affects Determination of Progression-Free Survival
Authors: Sullivan Daniel Carl , Schwartz Lawrence H. , Zhao Binsheng
Published: May 2013

Tumor measurements on computed tomgoraphic or MRI scans and/or the appearance of new lesions on any of a variety of imaging studies including positron emission tomographic scans are key determinants for assessing progression-free survival as an endpoint in many clinical trials of therapies for solid tumors. Test–retest tumor measurement reproducibility may vary considerably across serial scans on the same patient unless rigorous attention is paid to standardization of image acquisition parameters and unless measurements are made by trained, experienced observers using validated objective methods. Target lesion selection also must be done with care to choose lesions that are or will be reproducibly measurable. Likewise, new lesions will be missed or misinterpreted on follow-up imaging studies unless those imaging studies are obtained using techniques suitable for detecting early, small lesions. Reader variability is clearly a major component of the problem. The increasing availability of semiautomatic image processing algorithms will help ameliorate that issue. In addition, an array of internationally accepted guidelines, standards, and accreditation programs now exist to help address these problems. Clin Cancer Res; 19(10); 2621–8. ©2013 AACR.
Device-Related Thrombus Overlying a Left-Atrial Occlusion Device Implanted for Persistent Spontaneous Echo Contrast despite Prolonged Oral Anticoagulation Therapy
Authors: Elabbassi Wael , Osman Ahmed Najeeb , Chowdhury Mohammed Andaleeb , Nooryani Arif Al
Published: May 2013

A 75-year-old woman with a history of atrial fibrillation, severe biatrial enlargement, persistent dense spontaneous echo contrast in the left atrium and left-atrial appendage on appropriate oral anticoagulant therapy underwent implantation of the left-atrial occlusion device to decrease her risk of thromboembolic stroke. Six weeks later, a scheduled transesophageal echocardiography showed a partially mobile mass (4.1 × 2.1 cm) overlying the atrial surface of the device: a suspected thrombus. This report highlights the importance of follow-up examination and the limitation of this treatment modality among patients with persistent atrial fibrillation, large left atria and dense spontaneous echo contrast.
Discrepancies of HIV-1 Reverse Transcriptase Resistance Interpretation of Insertions and Deletions between Two Genotypic Algorithms
Authors: López-Lopes Giselle Ibette Silva , Lança André Minhoto , de Paula Ferreira João Leandro , Souza Luciana Oliveira , de Macedo Brígido Luís Fernando
Published: May 2013

Background: Bioinformatics algorithms have been developed for the interpretation of resistance from sequence submission, which supports clinical decision making. This study evaluated divergences of the interpretation of the genotyping in two commonly used algorithms, using sequences with indels of reverse transcriptase genes. Methods: Sequences were obtained from virus RNA of patients failing highly active antiretroviral therapy from 2004 to 2011. Alignments were obtained using Clustal W including subtype B consensus and HXB2. Sequences with evidence of indels were submitted to the Stanford Resistance Database and to the Geno2Pheno to locate indel positioning and determine the resistance profile. Results: A total of 1,959 partial reverse transcriptase sequences were assessed, mostly subtype B (74%). Insertions and deletions were observed in 0.9 and 0.6% of sequences, respectively. Discordant insert positioning was assigned for most (90%) insertion sequences, with 27% discordances for deletions. Susceptibility differed for some antiretroviral drugs, predominantly for TDF, d4T and ETV, when sequences with deletions were evaluated. Conclusion: Both indel positioning and its impact on drug susceptibility varies depending on the algorithm, a fact that might influence the clinical decision. Critical analysis of indel sequences with manual alignments is important, and its use alongside different algorithms may be important to better understand the outcomes of genotypic resistance prediction.
Chromosome Studies of European Cyprinid Fishes: Cross-Species Painting Reveals Natural Allotetraploid Origin of a Carassius Female with 206 Chromosomes
Authors: Knytl M. , Kalous L. , Symonová R. , Rylková K. , Ráb P.
Published: May 2013

A single female with 206 chromosomes and another 26 females with 156 chromosomes identified as Prussian carp, Carassius gibelio, and 5 individuals with 100 chromosomes identified as crucian carp, C. carassius, were sampled during field survey in one locality in the upper Elbe River. To identify the origin of females with high chromosome numbers, comparative karyotype analysis, GISH, with whole C. carassius DNA as probe and phylogenetic positions of sampled individuals revealed by cytochrome b mitochondrial marker were performed. GISH showed consistently bright labeling of 50 chromosomal elements out of 206, corresponding to the haploid chromosome number of C. carassius. The position of these females with high chromosome numbers in a reconstructed phylogenetic tree was within the clade of C. gibelio, documenting its affiliation to C. gibelio mitochondrial, i.e. maternal lineage. Our findings indicated that the mother of the female with high chromosome numbers was a gynogenetically reproducing 156-chromosome C. gibelio female and the father a bisexually reproducing C. carassius male. We, therefore, hypothesized that the C. gibelio × C. carassius allopolyploid female with 206 chromosomes arose by a mechanism of sperm genome addition to an unreduced egg of the mother.
Tracking Chromosome Evolution in Southern African Gerbils Using Flow-Sorted Chromosome Paints
Authors: Knight L.I. , Ng B.L. , Cheng W. , Fu B. , Yang F. , Rambau R.V.
Published: May 2013

Desmodillus and Gerbilliscus (formerly Tatera) comprise a monophyletic group of gerbils (subfamily Gerbillinae) which last shared an ancestor approximately 8 million years ago; diploid chromosome number variation among the species ranges from 2n = 36 to 2n = 50. In an attempt to shed more light on chromosome evolution and speciation in these rodents, we compared the karyotypes of 7 species, representing 3 genera, based on homology data revealed by chromosome painting with probes derived from flow-sorted chromosomes of the hairy footed gerbil, Gerbillurus paeba (2n = 36). The fluorescent in situ hybridization data revealed remarkable genome conservation: these species share a high proportion of conserved chromosomes, and differences are due to 10 Robertsonian (Rb) rearrangements (3 autapomorphies, 3 synapomorphies and 4 hemiplasies/homoplasies). Our data suggest that chromosome evolution in Desmodillus occurred at a rate of ∼1.25 rearrangements per million years (Myr), and that the rate among Gerbilliscus over a time period spanning 8 Myr is also ∼1.25 rearrangements/Myr. The recently diverged Gerbillurus (G. tytonis and G. paeba) share an identical karyotype, while Gerbilliscus kempi, G. afra and G. leucogaster differ by 6 Rb rearrangements (a rate of ∼1 rearrangement/Myr). Thus, our data suggests a very slow rate of chromosomal evolution in Southern African gerbils.
Equity in Public Health: An Epigenetic Perspective
Authors: Stapleton G. , Schröder-Bäck P. , Townend D.
Published: May 2013

Evidence emerging from the study of epigenetics and epigenomics challenges notions of health by enhancing understanding of disease etiologies and improving awareness of new health risks. New paradigms arising from epigenetic and epigenomic research present challenging cases through which to debate theories of justice in health because they expand the concept of health and, controversially, place value on what was previously assumed to be ‘healthy' individual variance. Discoveries of the dynamic nature of the epigenome and its variable sensitivity towards change in numerous phenomena add further complexity to the assessment of health inequalities. Such evidence can cast doubt on perceptions of justice in health, which in turn raises questions over the suitability of actions taken in pursuit of equity. This article discusses how recent developments in epigenetics and epigenomics may impact upon assessments of equity in health. A review of literature discussing possible health risks associated with acquired yet heritable epigenetic variance is used to highlight the diversity of possible pathways through which health may be influenced. From this context, the consideration of health risk with respect to epigenetics, it is argued, demands a more inclusive concept of health when used in discussions of inequities.
Genetic Analysis of Italian Patients with Congenital Hyperinsulinism of Infancy
Authors: Sogno Valin Paola , Proverbio Maria Carla , Diceglie Cecilia , Gessi Alessandra , di Candia Stefania , Mariani Benedetta , Zamproni Ilaria , Mangano Eleonora , Asselta Rosanna , Battaglia Cristina , Caruso-Nicoletti Manuela , Mora Stefano , Salvatoni Alessandro
Published: May 2013

Background/Aims: Congenital hyperinsulinism of infancy is a rare disease that needs prompt treatment to avoid brain damage. There are currently no data regarding the clinical and molecular features of Italian patients. Methods: Thirty-three patients with HI and their parents were included. Consanguinity was reported in six patients. Half of patients were macrosomic at birth. None had raised 3-hydroxybutyrylcarnitine or hyperammonemia. Molecular analysis of ABCC8 and KCNJ11 genes was performed in all patients, and subjects with no mutation underwent analysis of HNF4A and GCK. GLUD1 and HADH genes were analyzed in a patient with leucine sensitivity. Results: Mutations in the ABCC8 and KCNJ11 genes were found in 45% of the patients (6 novel). No mutations in HNF4A, GLUD1 and GCK genes were found. Recessive mode of inheritance was found in 21% of patients. A single heterozygous mutation was identified in 24% of probands. 72% of the patients were responsive to medical treatment, and 44% of the 17 patients with no identified mutation achieved spontaneous remission. Nine children, unresponsive to medical therapy, underwent pancreatectomy. Conclusion: This is the first report on hyperinsulinism of infancy in Italy, confirming the complexity of the clinical forms and the heterogeneity of the genetic causes of the disease.
Partial Trisomy 2p and Partial Monosomy 2q Arising from a Paternal Intrachromosomal 2q-into-2p Between-Arm Insertion and Paracentric Inversion: Molecular Cytogenetic Characterization of a Four-Break Rearrangement
Authors: Manolakos E. , Vetro A. , Papadopoulou E. , Kefalas K. , Lagou M. , Thomaidis L. , Peitsidis P. , Sifakis S. , Divane A. , Ziegler M. , Liehr T. , Zuffardi O. , Papoulidis I.
Published: May 2013

We report on a 26-month-old boy with an interstitial duplication of 2p22.3p22.2 and an interstitial deletion of 2q14.1q21.2. The abnormality was derived from his father having a balanced paracentric inversion and pericentric insertion. The deletion in the child was identified by cytogenetic analysis and characterized in more detail by molecular cytogenetics and array comparative genomic hybridization. The latter revealed a 20-Mb deletion in the long arm and a 5.6-Mb duplication in the short arm of chromosome 2. Fluorescence in situ hybridization in paternal chromosomes characterized an intrachromosomal insertion of 2q14.1q21.2 into 2p23; additionally a paracentric inversion of 2p13p23 was observed. The boy with the unbalanced karyotype suffered from severe psychomotor retardation, thrombophilia due to protein C deficiency, and hypertrophic cardiomyopathy and also had phenotypic abnormalities. Most of these features have previously been described in individuals with interstitial deletion of 2q14.1.
Unique Karyotype: mos 46,X,dic(X;Y)(p22.33;p11.32)/ 45,X/45,dic(X;Y)(p22.33;p11.32) in an Egyptian Patient with Ovotesticular Disorder of Sexual Development
Authors: Mazen I.M. , Kamel A.K. , Mohamed A.M. , Hussien H.A. , Essawi M.L. , Hassan H.A. , El-Ruby M.O. , Aref A. , Mekkawy M.K.
Published: May 2013

Ovotesticular disorder of sexual development (OT-DSD) is an unusual form of DSD, characterized by the coexistence of testicular and ovarian tissue in the same individual. In this report, we present clinical, cytogenetic and molecular data of an Egyptian patient with ambiguous genitalia and OT-DSD, who had a unique karyotype comprising 3 different cell lines: mos 46,X,dic(X;Y)(p22.33;p11.32)/45,X/ 45,dic(X;Y)(p22.33;p11.32). This mosaic karyotype probably represents 2 different events: abnormal recombination between the X and Y chromosomes during paternal meiosis and postzygotic abnormality in mitotic segregation of the dic(X;Y) chromosome, resulting in a mosaic karyotype. The presence of the sex-determining region Y (SRY) gene explains the development of testicular tissue. On the other hand, other factors, including the presence of a 45,X cell line, partial SRY deletion, X inactivation pattern, and position effect, could be contributed to genital ambiguity. Explanation of the patient's phenotype in relation to the genotype is discussed with a literature review. We conclude that FISH analysis with X- and Y-specific probes and molecular analysis of the SRY gene are highly recommended and allow accurate diagnosis for optimal management of cases with ambiguous genitalia.
Pancreatic Metastasis from Mixed Adenoneuroendocrine Carcinoma of the Uterine Cervix: A Case Report
Authors: Nishimura Chihiro , Naoe Hideaki , Hashigo Shunpei , Tsutsumi Hideharu , Ishii Shotaro , Konoe Takeyasu , Watanabe Takehisa , Shono Takashi , Sakurai Kouichi , Takaishi Kiyomi , Ikuta Yoshiaki , Chikamoto Akira , Tanaka Motohiko , Iyama Ken-ichi , Baba Hideo , Katabuchi Hidetaka , Sasaki Yutaka
Published: May 2013

Metastatic cancers of the pancreas are rare, accounting for approximately 2-4% of all pancreatic malignancies. Renal cell carcinoma is the most common solid tumor that metastasizes to the pancreas. Here, we present a case of uterine cervical carcinoma metastasizing to the pancreas and review the literature regarding this rare event. A 44-year-old woman with a uterine cervical tumor had undergone radical hysterectomy and had been diagnosed pathologically with stage Ib mixed adenoneuroendocrine carcinoma in 2004. She underwent concurrent radiotherapy and chemotherapy postoperatively. Pulmonary metastases subsequently appeared in 2008 and 2011, and she underwent complete resection of the lung tumors by video-assisted thoracic surgery. Although she was followed up without any treatment and with no other recurrences, positron emission tomography revealed an area of abnormal uptake within the pancreatic body in 2012. Enhanced computed tomography demonstrated a 20-mm lesion in the pancreatic body and upstream pancreatic duct dilatation. Endoscopic ultrasonography-guided fine needle aspiration was performed and pathological examination suggested neuroendocrine carcinoma (NEC). On the basis of these results and the patient's oncological background, lesions in the pancreatic body were diagnosed as secondary metastasis from the cervical carcinoma that had been treated 8 years earlier. No other distant metastases were visualized, and the patient subsequently underwent middle pancreatectomy. Pathological examination showed NEC consistent with pancreatic metastasis from the uterine cervical carcinoma. The patient has survived 7 months since the middle pancreatectomy without any signs of local recurrence or other metastatic lesions.
Postradiation Osteosarcoma in an Older Prostate Cancer Survivor: Case Study and Literature Review with Emphasis on Geriatric Principles
Authors: Gumber Divya , Rodin Miriam , Wildes Tanya M.
Published: May 2013

The aging population and the increasing number of cancer survivors will likely be associated with more second primary malignancies due to prior cancer treatment. Since the incidence of most cancers increases with age, these treatment-associated second malignancies will likely disproportionately impact older adults. Here, we present the case of a 78-year-old man with a history of localized prostate cancer treated with external beam radiation therapy 11 years prior, who developed osteosarcoma of the ilium. Geriatric screening showed a fit older male with few comorbidities, functional independence and no other geriatric syndromes. Given the patient's preference for a limb-sparing operation, neoadjuvant chemotherapy was undertaken. With the paucity of clinical trial data on osteosarcoma in older adults, the patient was given a regimen of carboplatin (substituted for cisplatin), doxorubicin and methotrexate. Unfortunately, he developed methotrexate-induced acute kidney injury. Chemotherapy was discontinued, and he proceeded to hemipelvectomy. His postoperative course was marked by numerous complications, including delirium, depression and recurrent hospitalizations. He ultimately developed a local recurrence and elected for hospice care. This case highlights the challenges of managing older adults with treatment-associated malignancies. Clinicians face a lack of clinical trial data from which to extrapolate limitations of therapeutic options because of prior therapy and a limited ability to precisely predict which elders will experience adverse outcomes. Better approaches are needed to help older patients make decisions which fulfill their goals of care and to improve the care of older adults with treatment-associated malignancies.
Impact of Onset-to-Reperfusion Time on Stroke Mortality
Authors: Mazighi Mikael , Chaudhry Saqib A. , Ribo Marc , Khatri Pooja , Skoloudik David , Mokin Maxim , Labreuche Julien , Meseguer Elena , Yeatts Sharon D. , Siddiqui Adnan H. , Broderick Joseph , Molina Carlos A. , Qureshi Adnan I. , Amarenco Pierre
Published: May 2013

Background—

Onset-to-reperfusion time has been reported to be associated with clinical prognosis. However, its impact on mortality remained to be assessed. Using a collaborative pooled analysis, we examined whether early mortality after successful endovascular treatment is time dependent.

Methods and Results—

In a collaborative pooled analysis of 7 endovascular databases, we assessed the impact of onset-to-reperfusion time in large-artery occlusion (internal carotid artery or middle cerebral artery) on outcomes. Successful reperfusion was defined as complete or partial restoration of blood flow within 8 hours from symptom onset. Primary outcome was 90-day all-cause mortality. Secondary outcomes included 90-day favorable outcome (modified Rankin Scale score, 0–2), 90-day excellent outcome (modified Rankin Scale score, 0–1), and occurrence of any intracerebral hemorrhage within 24 to 36 hours after treatment. A total of 480 cases with successful reperfusion (median time, 285 minutes) contributed to the present pooled analysis (120 with internal carotid artery occlusion and 360 with isolated middle cerebral artery occlusion). Increasing onset-to-reperfusion time was associated with an increased rate of mortality and intracerebral hemorrhage and with a decreased rate of favorable and excellent outcomes, without heterogeneity across studies. The adjusted odds ratio for each 30-minute time increase was 1.21 (95% confidence interval, 1.09–1.34;
P
<0.001) for mortality, 0.79 (95% confidence interval, 0.72–0.87) for favorable outcome, 0.78 (95% confidence interval, 0.71–0.86) for excellent outcome, and 1.21 (95% confidence interval, 1.10–1.33) for intracerebral hemorrhage.

Conclusion—

Onset-to-reperfusion time affects mortality and favorable outcome and should be considered the main goal in acute stroke patient management.
Taxonomy and redescription of the Yellow-footed Antechinus, Antechinus flavipes (Waterhouse) (Marsupialia: Dasyuridae)
Authors: BAKER ANDREW M. , DYCK STEVE VAN
Published: May 2013

We provide a taxonomic redescription of the ubiquitous and variable dasyurid marsupial Yellow-footed Antechinus, Antechinus flavipes (Waterhouse), which comprises three currently recognized subspecies whose combined geographic distribution spans almost the length and breadth of Australia. A. flavipes leucogaster Gray is confined to south-west Western Australia; A. flavipes flavipes is distributed in south-eastern Australia across four states—South Australia, Victoria, New South Wales and Queensland; A. flavipes rubeculus Van Dyck is confined to the wet tropics of Queensland. A. flavipes is readily distinguished from all extant congeners based on external morphology by the following combination of features: a grey head; orange-yellow toned flanks/rump, feet and tail base; pale eye-rings and a darkened tail tip. A. flavipes skulls are stout, being broad at the level of the rear upper molars, have small palatal vacuities and small entoconid cusps on the lower molars. However, notable differences among subspecies of A. flavipesprevent any obvious collection of skull characters being diagnostic for species-level discrimination among congeners. A. flavipes rubeculus is the largest of the three subspecies of Yellow-footed Antechinus and most similar in skull morphology to A. leo, A. bellus and A. godmani—all four species are geographically limited to tropical Australia. A. f. rubeculus is notably larger in many characters than its conspecifics: A. f. flavipes, the next largest, and A. f. leucogaster, the smallest of the group. A. f. flavipes and A. f. leucogaster diverge significantly at only a few skull characters, and both subspecies have cranial morphological affinities with the recently discovered A. mysticus, most notably A. f. leucogaster. Phylogenies generated from mt- and nDNA data strongly support Antechinus flavipes as monophyletic with respect to other members of the genus; within A. flavipes, each of the three recognized subspecies form distinctive monophyletic clades.
Comparison of Monthly Temperature Extremes Simulated by CMIP3 and CMIP5 Models
Authors: Yao Yao , Luo Yong , Huang Jianbin , Zhao Zongci
Published: May 2013

The extreme monthly-mean temperatures simulated by 28 models in the fifth phase of the Coupled Model Intercomparison Project (CMIP5) are evaluated and compared with those from 24 models in the third phase of the Coupled Model Intercomparison Project (CMIP3). Comparisons with observations and reanalyses indicate that the models from both CMIP3 and CMIP5 perform well in simulating temperature extremes, which are expressed as 20-yr return values. When the climatological annual cycle is removed, the ensemble spread in CMIP5 is smaller than that in CMIP3. Benefitting from a higher resolution, the CMIP5 models perform better at simulating extreme temperatures on the local gridcell scale. The CMIP5 representative concentration pathway (RCP4.5) and CMIP3 B1 experiments project a similar change pattern in the near future for both warm and cold extremes, and the pattern is in agreement with that of the seasonal extremes. By the late twenty-first century, the changes in monthly temperature extremes projected under the three CMIP3 (B1, A1B, and A2) and two CMIP5 (RCP4.5 and RCP8.5) scenarios generally follow the changes in climatological annual cycles, which is consistent with previous studies on daily extremes. Compared with the CMIP3 ensemble, the CMIP5 ensemble shows a larger intermodel uncertainty with regard to the change in cold extremes in snow-covered regions. Enhanced changes in extreme temperatures that exceed the global mean warming are found in regions where the retreat of snow (or the soil moisture feedback effect) plays an important role, confirming the findings for daily temperature extremes.
Observational Evidence That Enhanced Subsidence Reduces Subtropical Marine Boundary Layer Cloudiness
Authors: Myers Timothy A. , Norris Joel R.
Published: May 2013

Conventional wisdom suggests that subsidence favors the presence of marine stratus and stratocumulus because regions of enhanced boundary layer cloudiness are observed to climatologically co-occur with regions of enhanced subsidence. Here it is argued that the climatological positive correlation between subsidence and cloudiness is not the result of a direct physical mechanism connecting the two. Instead, it arises because enhanced subsidence is typically associated with stronger temperature inversions capping the marine boundary layer, and stronger temperature inversions favor greater cloudiness. Through statistical analysis of satellite cloud data and meteorological reanalyses for the subsidence regime over tropical (30°S–30°N) oceans, it is shown that enhanced subsidence promotes reduced cloudiness for the same value of inversion strength and that a stronger inversion favors greater cloudiness for the same value of subsidence. Using a simple conceptual model, it is argued that enhanced subsidence leads to reduced cloud thickness, liquid water path, and cloud fraction by pushing down the top of the marine boundary layer. Moreover, a stronger inversion reduces entrainment drying and warming, thus leading to a more humid boundary layer and greater cloud thickness, liquid water path, and cloud fraction. These two mechanisms typically oppose each other for geographical and seasonal cloud variability because enhanced subsidence is usually associated with stronger inversions. If global warming results in stronger inversions but weaker subsidence, the two mechanisms could both favor increased subtropical low-level cloudiness.
Assimilation of Satellite Infrared Radiances and Doppler Radar Observations during a Cool Season Observing System Simulation Experiment
Authors: Jones Thomas A. , Otkin Jason A. , Stensrud David J. , Knopfmeier Kent
Published: May 2013

An observing system simulation experiment is used to examine the impact of assimilating water vapor–sensitive satellite infrared brightness temperatures and Doppler radar reflectivity and radial velocity observations on the analysis accuracy of a cool season extratropical cyclone. Assimilation experiments are performed for four different combinations of satellite, radar, and conventional observations using an ensemble Kalman filter assimilation system. Comparison with the high-resolution “truth” simulation indicates that the joint assimilation of satellite and radar observations reduces errors in cloud properties compared to the case in which only conventional observations are assimilated. The satellite observations provide the most impact in the mid- to upper troposphere, whereas the radar data also improve the cloud analysis near the surface and aloft as a result of their greater vertical resolution and larger overall sample size. Errors in the wind field are also significantly reduced when radar radial velocity observations were assimilated. Overall, assimilating both satellite and radar data creates the most accurate model analysis, which indicates that both observation types provide independent and complimentary information and illustrates the potential for these datasets for improving mesoscale model analyses and ensuing forecasts.
Balancing paid work, care and leisure in post-separation households
Authors: Bakker Wilma , Karsten Lia
Published: May 2013

This article provides insight into the daily lives of separated parents involved in two types of living arrangements: single parents (mainly mothers) living with their children full-time and co-parents living with their children part-time. Earlier studies have stated that the everyday lives of separated mothers are more constrained than those of married mothers. We show that the growing diversity of post-separation living arrangements should no longer be ignored in studies of the consequences of separation, in policy frameworks or in debates on separation. Our findings reveal that single mothers experience more constraints in combining work, care and leisure in daily life than co-parents do. The differences between the groups are explained by different commitments in the work and care domains. These differences are not solely matters of choice. Single mothers who are less highly educated and work fewer hours than co-parents have limited resources with which to arrange or negotiate a more gender-equal outcome. Empirical evidence is drawn from individual in-depth interviews with 18 separated parents living in The Netherlands.
Sick leave before, during and after pregnancy
Authors: Rieck Karsten Marshall Elseth , Telle Kjetil
Published: May 2013

Using register data on every employed Norwegian woman giving birth to her first child in the period 1995–2008, we describe sick leave before, during and after pregnancy. Sick leave increases abruptly in the month of conception and continues to grow throughout the pregnancy. Compared to pre-pregnancy levels, sick leave of pregnant women has risen substantially since the mid-1990s. In line with hypotheses of women’s ‘double burden’, observed sick-leave rates increase in the years after birth. However, when sick leave during a succeeding pregnancy is excluded, the increase in women’s sick leave in the years after birth dissolves.
Contrast-enhanced US quantitatively detects changes of tumor perfusion in a murine breast cancer model during adriamycin chemotherapy
Authors: Wang Jian-wei , Cao Long-hui , Han Feng , Zheng Wei , Chen Yao , Li An-hua , Zhou Jian-hua
Published: May 2013

Background

Currently used morphologic criteria have limitations in assessing tumor response to chemotherapy because of the relatively slow tumor shrinkage as measured by conventional morphologic imaging. Functional imaging techniques show promising results in early assessment of tumor response to treatment.

Purpose

To quantitatively detect changes in tumor perfusion during chemotherapy with contrast-enhanced ultrasound.

Material and Methods

Twenty-three MCF-7 breast cancer bearing nude mice treated by either adriamycin ( n = 11) or sterile saline ( n = 12) were imaged before and after treatment with an ultrasound scanner after bolus injection of SonoVue. Regions of interest within the tumor were analyzed offline to determine perfusion parameters including peak enhancement (PE), area under the curve of wash-in (WiAUC), rise time (RT), wash-in rate (WiR), wash-in perfusion index (WiPI), and quality of fit (QOF). Hematoxylin and eosin was used to assess tumor cell density and immunohistochemical analysis was performed for evaluation of microvascular density (MVD).

Results

Treatment with adriamycin significantly reduced tumor growth in comparison to the control group ( P < 0.001). There was no significant difference in perfusion parameters before treatment. Treatment with adriamycin resulted in a significant decrease in PE, WiAUC, WiR, and WiPI in comparison with control group ( P < 0.01). The tumor cell density estimated by pathology slice was significantly lower in treated tumors than in control tumors after treatment ( P < 0.001). Immunohistochemistry showed significant decreases of MVD in treated tumors as compared with control tumors ( P < 0.001) after treatment.

Conclusion

Quantitative contrast-enhanced ultrasound can detect the change of tumor perfusion after chemotherapy, which may enable early assess tumor response to chemotherapy.
Pearls and pitfalls in experimental models of spreading depression
Authors: Ayata Cenk
Published: May 2013

Background

Spreading depression (SD) is the electrophysiological substrate of migraine aura and a potential trigger for headache. Since its discovery by Leão in 1944, SD has transformed from being viewed as an epiphenomenon into a therapeutic target relevant in the pathophysiology of migraine and brain injury.

Aim

Despite decades of research, the underpinnings of SD are still poorly understood, hampering our efforts to selectively block its initiation and spread. Experimental models have nevertheless been useful to measure the likelihood of SD occurrence (i.e. SD susceptibility) and characterize genetic, physiological and pharmacological modulation of SD in search of potential therapies, such as in migraine prophylaxis and stroke. Here, I review experimental SD susceptibility endpoints and surrogates, and minimum essential model requirements to improve their utility in drug screening.

Conclusion

A critical reappraisal of strengths and caveats of experimental models of SD susceptibility is needed to set standards and improve data quality, interpretation and reconciliation.
Pearls and pitfalls in human pharmacological models of migraine: 30 years' experience
Authors: Ashina Messoud , Hansen Jakob Møller , Olesen Jes
Published: May 2013

In vitro studies have contributed to the characterization of receptors in cranial blood vessels and the identification of new possible anti-migraine agents. In vivo animal models enable the study of vascular responses, neurogenic inflammation, peptide release and genetic predisposition and thus have provided leads in the search for migraine mechanisms. All animal-based results must, however, be validated in human studies because so far no animal models can predict the efficacy of new therapies for migraine.

Given the nature of migraine attacks, fully reversible and treatable, the headache- or migraine-provoking property of naturally occurring signaling molecules can be tested in a human model. If such an endogenous substance can provoke migraine in human patients, then it is likely, although not certain, that blocking its effect will be effective in the treatment of acute migraine attacks.

To this end, a human in vivo model of experimental headache and migraine in humans has been developed. Human models of migraine offer unique possibilities to study mechanisms responsible for migraine and to explore the mechanisms of action of existing and future anti-migraine drugs. The human model has played an important role in translational migraine research leading to the identification of three new principally different targets in the treatment of acute migraine attacks and has been used to examine other endogenous signaling molecules as well as genetic susceptibility factors. New additions to the model, such as advanced neuroimaging, may lead to a better understanding of the complex events that constitute a migraine attack, and better and more targeted ways of intervention.
Teleology Revived? Cooperation and the Ends of Nature
Authors: Oliver Simon
Published: May 2013

Modern natural science and philosophies of nature are often hostile to the notion of teleology in nature. Nevertheless, teleological orientation is ascribed to human behaviour because such behaviour is deliberative and intentional. This establishes a dualism between nature and culture, but also between intentional mind and inert matter. This essay argues that such dualisms are overcome by resisting a distinction between ‘extrinsic’ teleology and ‘intrinsic’ teleology, and by recovering Aristotle’s connection between teleology and form. Recent work on autopoiesis in the philosophy of mind indicates overlap with Aristotelian form. Finally, the new category of cooperation applied first to human behaviour in the realm of game theory, and latterly to evolution, indicates ways in which normative descriptions of nature understood teleologically are once again possible.
The Natural Law and the Normative Significance of Nature
Authors: Porter Jean
Published: May 2013

We regard cooperation as generally good, and yet this does not imply that it is morally good. The scholastic conception of nature offers the kind of distinction between levels of normative appraisal that we need, and suggests a fruitful way of thinking about the moral significance of our naturally sociable nature.
A Kantian Response to Jean Porter
Authors: Hare John
Published: May 2013

Jean Porter’s natural law theory and my divine command theory differ less than one might expect. Two differences that remain are that, with respect to deductivism, the view that we can deduce our moral obligations from human nature, we agree that human nature is insufficiently specific, but she does not acknowledge the place of revealed divine law in later scholasticism or the role for what Scotus calls ‘dispensations’. With respect to eudaimonism, the view that our choices are for the sake of happiness, I do not agree that life presents itself to us integrated under the conception of a single way of life. Even in Aquinas there is a tension between his eudaimonism and his view that the love of God for God’s own sake is the distinctive mark of charity, and that charity toward the neighbor requires us to promote the neighbor’s good for the neighbor’s sake and not our own.
Philosophical Comments on Ahmed’s Proposal
Authors: Hare John
Published: May 2013

Arif Ahmed’s paper claims moral neutrality for game theory. This is not true, however, of much of classical game theory, for example Ken Binmore’s Game Theory and the Social Contract (1994). The field has changed comparatively recently. With respect to his own version, he claims that evolutionary explanation of cooperation is incompatible with theism, but this is because he thinks just about anything is compatible with it. It is important to see that this critique is the same as the logical positivists’ critique in the 1950s, for example in Antony Flew’s parable of the invisible gardener. The logical positivists thought that a statement could only be meaningful if it is either a tautology or empirically verifiable or falsifiable. But a claim that God exists is not subject to empirical confirmation, because God is not that kind of being. To dismiss the claim on that basis is just to beg the question.
Convergence, Incommensurability, Contradiction, or Overlapping Consensus? A Response to Daniel Weiss
Authors: Helmer James E.
Published: May 2013

Contemporary religious and scientific perspectives make various metaphysical truth claims that are frequently perceived to be either competitive or contradictory. Two dominant approaches that have been employed to explain and to resolve such conflicts are those of convergence, where one view trumps over and assimilates the other, and incommensurability, where the views in question come to be regarded as actually non-competitive. Drawing on recent models of inter-religious dialogue, in his essay, ‘The Fruits of Contradiction: Evolution, Cooperation and Ethics in an Inter-Religious Context’, Daniel Weiss proposes by way of analogy a third approach, that of critical yet constructive interaction between religious and secular ethical perspectives where metaphysically contradictory commitments remain held in unresolved tension. In this essay, I engage Weiss’s proposal and raise questions about the analogy that he develops. Drawing on the political theory of Rawlsian liberalism, I propose a fourth conceptuality—that of overlapping consensus—which I argue bears important similarities to the model that Weiss advocates.
Evolution, Cooperation and Ethics: Some Methodological and Philosophical Hurdles
Authors: Coakley Sarah
Published: May 2013

Secular evolutionary theory presents a profound challenge to theological ethics in pressing the question of how ethics is related to derived instincts. As an introduction to the essays that follow, the meaning and significance of evolutionary cooperation is here briefly set out along with a sketch of some dangers attending the exploration.
‘It’s all red ink’: The interpretation of biblical metaphor among Evangelical Christian YouTube users
Authors: Pihlaja Stephen
Published: May 2013

Among Evangelical Christians on the popular video-sharing site YouTube, the Bible is an important resource for justifying and challenging specific words and actions. Such justifications and challenges provide researchers with an opportunity to study how authoritative text is interpreted in social interaction. To that end, this article presents analysis of a single debate – an episode of what YouTube users call ‘drama’ – around one Evangelical Christian’s controversial use of a passage from the Bible to justify calling others ‘human garbage’. This analysis shows first, that conflicting interpretations and use of the Bible’s moral authority led to the development of ‘drama’ because users evidenced differing beliefs about the development of biblical metaphorical language; and second, that users appropriated the Bible’s words to their own discourse activity through exegesis and metaphor development. This article thus provides both an empirical case study in the interpretation of figurative language and a challenge to the common assumption that Evangelical Christians are committed to a ‘literal’ interpretation of the Bible.
Deletion of the NF-κB subunit p65/RelA in the hematopoietic compartment leads to defects in hematopoietic stem cell function
Authors: Stein Sarah J. , Baldwin Albert S.
Published: May 2013

Key Points

p65 is an important factor in hematopoiesis through the regulation of hematopoietic stem cell function and lineage commitment. p65 controls the expression of genes encoding key factors that promote hematopoietic stem cell homeostasis.
Genetic analysis and epidemiology of Crimean Congo hemorrhagic fever viruses in Baluchistan province of Pakistan
Authors: Alam Muhammad Masroor , Khurshid Adnan , Sharif Salmaan , Shaukat Shahzad , Rana Muhammad Suleman , Angez Mehar , Zaidi Syed Sohail Zahoor
Published: May 2013

Background

Pakistan is considered as an endemic country for Crimean-Congo Hemorrhagic fever with numerous outbreaks and sporadic cases reported during the past two decades. Majority of cases are reported from Baluchistan province with subsequent transmissions to non-endemic regions mainly through infected animals directly or via infested ticks. We hereby describe the molecular investigations of CCHF cases reported during 2008 in Quetta city of Baluchistan province.

Methods

Serum Samples from 44 patients, with clinical signs of hemorrhagic fever attending a tertiary care hospital in Quetta city, were collected and tested for CCHF virus antigen and genomic RNA, using capture IgM EIA kit and standard RT-PCR assay, respectively. The partial S-gene fragments were directly sequenced to get information related to the prevailing CCHFV genotypes and their molecular epidemiology in Pakistan.

Results

Out of the total forty four, sixteen (36%) samples were found positive for CCHF IgM. Similarly, viral RNA was detected in six (16%) samples. Phylogenetic analysis revealed that all study viruses belong to genotype Asia-1 with closest similarity (99-100%) to the previously reported strains from Pakistan, Afghanistan and Iran.

Conclusion

We conclude that CCHF virus remains endemic within Baluchistan and its neighboring regions of Afghanistan warranting a need of incessant surveillance activities.
Methods to increase participation in organised screening programs: a systematic review
Authors: Camilloni Laura , Ferroni Eliana , Cendales Beatriz Jimenez , Pezzarossi Annamaria , Furnari Giacomo , Borgia Piero , Guasticchi Gabriella , Rossi Paolo Giorgi ,   the Methods to increase participation Working Group
Published: May 2013

Background

The European Community recommends the implementation of population-based screening programmes for cervical, breast, and colorectal cancers. This recommendation is supported by many observational studies showing that organised programmes effectively reduce mortality and control the inappropriate use of screening tests. We conducted a systematic review of studies assessing the efficacy of interventions to increase participation in organised population-based screening programs.

Methods

We included all studies on interventions aimed at increasing screening participation published between 1/1999 and 7/2012. For those published before 1999, we considered the Jepson et al. (2000) review (Health Technol Assess 4:1-133, 2000).

Results

Including studies from the Jepson review, we found 69 with quantitative information on interventions in organised screening: 19 for cervical, 26 for breast, 20 colorectal cancers, and 4 for cervical and breast cancer together.

Effective interventions were: postal (breast RR = 1,37 95% Confidence Interval (95% CI): 1.25-1.51; cervical RR = 1.71 95% CI: 1.60-1.83; colorectal RR = 1.33 95% CI: 1.17-1.51) and telephone reminders (with heterogeneous methods for implementation); GP’s signature on invitation letter (breast RR = 1.13 95% CI: 1.11-1.16; cervical RR = 1.20 95% CI: 1.10-1.30; colorectal RR = 1.15 95% CI: 1.07-1.24); scheduled appointment instead of open appointment (breast RR = 1.26 95% CI: 1.02-1.55; cervical RR = 1.49 95% CI: 1.27-1.75; colorectal RR = 1.79 95% CI: 1.65-1.93). Mailing a kit for self-sampling cervical specimens increased participation in non-responders (RR = 2.37 95% CI: 1.44-3.90).

Conclusion

Although some interventions did prove to be effective, some specific variables may influence their effectiveness in and applicability to organised population-based screening programs.
The impact of discrete modes of spinal cord injury on bladder muscle contractility
Authors: Seth Abhishek , Chung Yeun Goo , Kim Daniel , Ramachandran Aruna , Cristofaro Vivian , Gomez III Pablo , Tu Duong , Huang Lin , Benowitz Larry I , Di Vizio Dolores , Sullivan Maryrose P , Adam Rosalyn M
Published: May 2013

Background

Prior studies have compared the effect of spinal cord injury elicited using distinct approaches on motor and visceral function. However, the impact of such discrete modes of injury specifically on bladder muscle contractility has not been explored in detail. The goal of this study is to compare the impact of complete spinal cord transection versus clip compression at thoracic vertebra eight (T8) on bladder muscle contractility.

Methods

Rats underwent no treatment (Control), laminectomy (Sham, SH); complete extradural transection (TX); or cord compression with an aneurysm clip (CX). Bladders and spinal cords were harvested at 6 wk for contractility studies or histological analysis.

Results

Detrusor strips from TX and CX rats showed higher spontaneous activity than those from SH rats. Furthermore, the duration of the neurally-mediated contractile response was longer in TX and CX rats compared to controls and showed attenuated relaxation. No significant differences were observed between muscle strips from SH, TX or CX rats in response to KCl, ATP or phenylephrine. However, tissues from TX and CX rats showed a higher sensitivity to carbachol compared to that from SH animals.

Conclusions

Complete SCI in rats either by cord transection or compression elicits qualitatively similar changes in bladder muscle contractility. Whereas cord transection is arguably easier to perform experimentally, cord compression better models the situation observed clinically, such that each approach has clear advantages and limitations.