bluuebunny/crossref_metadata_2025 huggingface dataset:
The power of possibility: causal learning, counterfactual reasoning, and pretend play
Authors: Buchsbaum Daphna , Bridgers Sophie , Skolnick Weisberg Deena , Gopnik Alison
Published: June 2012

We argue for a theoretical link between the development of an extended period of immaturity in human evolution and the emergence of powerful and wide-ranging causal learning mechanisms, specifically the use of causal models and Bayesian learning. We suggest that exploratory childhood learning, childhood play in particular, and causal cognition are closely connected. We report an empirical study demonstrating one such connection—a link between pretend play and counterfactual causal reasoning. Preschool children given new information about a causal system made very similar inferences both when they considered counterfactuals about the system and when they engaged in pretend play about it. Counterfactual cognition and causally coherent pretence were also significantly correlated even when age, general cognitive development and executive function were controlled for. These findings link a distinctive human form of childhood play and an equally distinctive human form of causal inference. We speculate that, during human evolution, computations that were initially reserved for solving particularly important ecological problems came to be used much more widely and extensively during the long period of protected immaturity.
A new hybrid organic–inorganic chain: [(phen)Cu–μ-(κ2O:O′-VP2O10H3)2–Cu(phen)]n
Authors: Venegas-Yazigi Diego , Vega Andres , Valdes de la Barra Karen , Saldias Marianela , Le Fur Eric
Published: June 2012

The structure of the title compound, poly[(dihydrogenphosphato-κO)(μ3-hydrogenphosphato)di-μ-oxido-(1,10-phenanthroline)copper(II)vanadium(V)], [CuV(HPO4)(H2PO4)O2(C12H8N2)]n, is defined by [(phen)Cu–μ-(κ2O:O′-VP2O10H3)2–Cu(phen)] units (phen is 1,10-phenanthroline), which are connected to neighbouring units through vanadyl bridges. Neighbouring chains have no covalent bonds between them, although they interdigitate through the phen groupsviaπ–π interactions.
Critical roles of the cAMP‐responsive element‐binding protein‐mediated pathway in disorganized epithelial phenotypes caused by mitochondrial dysfunction
Authors: Shibanuma Motoko , Ishikawa Fumihiro , Kobayashi Masayuki , Katayama Kazufumi , Miyoshi Hiroyuki , Wakamatsu Masami , Mori Kazunori , Nose Kiyoshi
Published: June 2012

In most human cancers, somatic mutations have been identified in the mtDNA; however, their significance remains unclear. We recently discovered that NMuMG mouse mammary epithelial cells, when deprived of mitochondria or following inhibition of respiratory activity, undergo epithelial morphological disruption accompanied with irregular edging of E‐cadherin, the appearance of actin stress fibers, and an altered gene expression profile. In this study, using the mtDNA‐less pseudo ρ0 cells obtained from NMuMG mouse mammary epithelial cells, we examined the roles of two mitochondrial stress‐associated transcription factors, cAMP‐responsive element‐binding protein (CREB) and C/EBP homologous protein‐10 (CHOP), in the disorganization of epithelial phenotypes. We found that the expression of matrix metalloproteinase‐13 and that of GADD45A, SNAIL and integrin α1 in the ρ0 cells were regulated by CHOP and CREB, respectively. Of note, knockdown and pharmacological inhibition of CREB ameliorated the disrupted epithelial morphology. It is interesting to note that the expression of high mobility group AT‐hook 2 (HMGA2), a non‐histone chromatin protein implicated in malignant neoplasms, was increased at the protein level through the CREB pathway. Here, we reveal how the activation of the CREB/HMGA2 pathway is implicated in the repression of integrin α1 expression in HepG2 human cancer cells, highlighting the importance of the CREB/HMGA2 pathway in malignant transformation associated with mitochondrial dysfunction, thereby raising the possibility that the pathway indirectly interferes with the cell–cell adhesion structure by influencing the cell–extracellular matrix adhesion status. Overall, the data suggest that mitochondrial dysfunction potentially contributes to neoplastic transformation of epithelial cells through the activation of these transcriptional pathways.
Review article: non‐malignant haematological complications of anti‐tumour necrosis factor alpha therapy
Authors: Bessissow T. , Renard M. , Hoffman I. , Vermeire S. , Rutgeerts P. , Van Assche G.
Published: June 2012

Background

Tumour necrosis factor‐alpha (TNF‐α) is an important mediator of the molecular cascade leading to chronic inflammation. TNF‐α inhibitors have proven their safety and efficacy in the treatment of inflammatory diseases.

Aim

To review the non–malignant haematological adverse events, such as thrombocytopaenia, neutropaenia, hypercoagulability, pancytopaenia and aplastic anaemia in patients receiving TNF‐α inhibitors.

Methods

We reviewed the literature by searching MEDLINE and EMBASE databases as well as references of all retrieved articles for the following terms: anti‐tumour necrosis factor, anti‐TNF, infliximab, adalimumab, certolizumab, etanercept, haematological complications, thrombocytopaenia, neutropaenia, anaemia, bone marrow and thrombosis.

Results

Thombocytopaenia is a very rare phenomenon and was associated with no serious adverse events. However, transient neutropaenia developed in up to 16% of cases. Patients with a previous history of neutropaenia on other therapies or baseline neutrophil count <4 × 109/L are at a particularly higher risk. The association between anti‐TNF‐α therapy and thrombosis is very nebulous due to the multitude of potential confounders. Only one case of primary eosinophilia has been reported with anti‐TNF‐α therapy.

Conclusion

Regular monitoring of the white blood cell count at baseline and with each infusion is recommended for patients on anti‐TNF‐α. Further studies to elucidate their interaction with the immune system are warranted.
Clinical trial design in haemophilia
Authors: DIMICHELE D. M. , BLANCHETTE V. , BERNTORP E.
Published: June 2012

Summary.  Progress in the evidence‐based care of haemophilia A and B worldwide has been historically challenged by the dearth of evaluable outcome data, including but not limited to the safety and effectiveness of therapeutic interventions. These challenges are partially rooted in the inherent difficulty of conducting prospective clinical trials and observational studies with statistically meaningful endpoints in a rare disease such as haemophilia. Despite the logistical barriers, the need for outcome data has never been more critical than in this time of expansive therapeutic advance tempered by the shrinking economic capacity to fund the rapidly increasing cost of treatment. Given that systematic analyses of published literature have been largely unsuccessful in compensating for the lack of rigorous and purposeful data collection, new approaches to clinical study design and statistical modelling are urgently needed. However, even as these are considered, the lack of broadly accepted and well‐defined clinical outcome endpoints poses an additional barrier to progress. The three presentations encompassed by this paper highlight the timely need for quality data from the perspectives of the clinicians, regulatory agencies and health care funders, and describe the ongoing coordinated efforts by the international haemophilia community to further understand and dismantle the barriers to harmonized and standardized data collection on a global scale using well‐defined clinical outcome endpoints.
Prevention and prediction of inhibitor risk
Authors: ASTERMARK J.
Published: June 2012

Summary.  Studies of determinants of the development of inhibitory antibodies in patients with haemophilia indicate that this is a complex process involving several factors. The foundation is characterized by the T‐ and B‐cell repertoire and the antigen presenting cells and to elicit an immune response to the deficient factor, a pre‐disposing foundation is needed. Hence, in the absence of a certain set of circumstances, there will be no risk for development of inhibitors. Conversely, in patients fundamentally at risk, genetic and non‐genetic factors might add to the risk. These factors may be additive or interactive, and ultimately promote or counteract the immune reaction by modifying immune regulators and the cytokine profile in an individual. In some subjects, only minor inflammatory signals might be needed, whereas in others a more pronounced pro‐inflammatory state will be required. Regarding genetic markers other than the type of mutation and the HLA class II molecules, polymorphisms in various immune regulatory genes have been associated with inhibitor risk. These associations have not, however, been consistent across all patient groups. The reason for this is not clear, but could be related to study design or statistical power, family relationships among those studied, the complexity of interacting molecules and ethnic genomic variation. The Hemophilia Inhibitor Genetics Study (HIGS) has identified additional candidates within the intracellular pathways, all of which require additional evaluation to be fully appreciated. In the case of non‐genetic factors, the overall view is that immune system challenges might add to the risk. HIGS data suggest that it will be possible to calculate a genetic score to identify patients at high risk for inhibitor development before the start of treatment. By doing so, it may hopefully be possible in the future to prevent the formation of inhibitors in these patients by offering therapeutic options other than the native factor VIII or IX molecule in an inflammatory setting.
Genetics of haemostasis
Authors: GOODEVE A. C. , PERRY D. J. , CUMMING T. , HILL M. , JENNINGS I. , KITCHEN S. , WALKER I. , GRAY E. , JAYANDHARAN G. R. , TUDDENHAM E.
Published: June 2012

Summary.  Congenital defects of platelets or plasma proteins involved in blood coagulation generally lead to bleeding disorders. In some of these disorders, patients with a severe phenotype are prone to spontaneous bleeds with critical consequences. This situation occurs more commonly in haemophilia A and haemophilia B and to a certain extent in severe forms (type 3) of von Willebrand disease. Defects in other plasma coagulation proteins and platelet factors are relatively rare, with an incidence of ≤1: 1–2 million. Molecular genetic studies of the human coagulation factors, especially factors VIII and IX, have contributed to a better understanding of the biology of these genetic disorders, the accurate detection of carriers and genetic counselling, and have also fostered new therapeutic strategies. This article reviews the evolution of genetics over the last five decades as a tool for bleeding disorder investigations, the recent advances in molecular techniques that have contributed to improved genetic diagnosis of this condition, and the development and utility of proficiency testing programmes and reference materials for genetic diagnosis of bleeding disorders.
Rare bleeding disorders
Authors: PEYVANDI FLORA , BOLTON‐MAGGS PAULA HB , BATOROVA ANGELIKA , DE MOERLOOSE PHILIPPE
Published: June 2012

Summary.  Rare bleeding disorders (RBDs) include the inherited deficiencies of fibrinogen, factor (F)II, FV, FV+FVIII, FVII, FX, FXI and FXIII. There have been remarkable advances in understanding the molecular profiles that lead to each type of coagulation factor deficiency. However, as a consequence of their rarity, clinical data regarding the characteristics of bleeding symptoms and their management remain limited. The clinical manifestations in different RBDs are heterogeneous, and the residual plasma coagulant factor level does not always predict bleeding tendency. In this review, we describe the general features and recent advances in understanding three such deficiencies: FXI, FVII and fibrinogen deficiencies.
Global haemostasis and point of care testing
Authors: DARGAUD Y. , SORENSEN B. , SHIMA M. , HAYWARD C. , SRIVASTAVA A. , NEGRIER C.
Published: June 2012

Summary.  The evaluation of the coagulation profile has used so far either clotting‐based or chromogenic assays with different endpoints. Clotting‐based techniques are the most used worldwide, and they certainly are useful for diagnosis of clotting factor deficiencies. However, the information provided is relatively limited, and therefore the individual profile of coagulation is poorly assessed. This is reflected by the weak correlation between the results of these assays and the clinical phenotype. Among the assays that benefited from technological advances, thrombin generation and thromboelastography are probably the most actively investigated, but they require specific instruments and are not fully automated. Their standardisation level is rapidly progressing, and they are progressively entering the clinical scene, with the attempt to provide additional information on the coagulation process and a meaningful clinical correlation. These inherited bleeding disorders frequently require replacement therapy using clotting factor concentrates that increase the plasma level of the missing clotting factor. The classical adjustment of the therapy is mainly based on the measurement of the plasma clotting activity of the protein administered. If one considers that a certain level of thrombin generated would predict clinical efficacy, monitoring of thrombin formation might offer new possibilities to individually predict the bleeding phenotype, select the most adapted therapeutic product and tailor the dose. The same holds true for thromboelastography/thromboelastometry which evaluate fibrin formation as well as clot resistance to fibrinolytic challenge, one step further down in the coagulation process. In this regard, these 2 assays could be seen as complementary in terms of information provided on the coagulation profile at the individual level.
Discordance between anaplastic lymphoma kinase status in primary non‐small‐cell lung cancers and their corresponding metastases
Authors: Kim Hyojin , Xu Xianhua , Yoo Seol‐Bong , Sun Ping‐Li , Jin Yan , Paik Jin Ho , Choe Gheeyoung , Jheon Sanghoon , Lee Choon‐Taek , Chung Jin‐Haeng
Published: June 2012

Aims:  The anaplastic lymphoma kinase gene (ALK) has attracted considerable attention as a potential molecular target in non‐small‐cell lung cancer (NSCLC). However, it is unclear whether ALK alterations are acquired during the metastatic progression of NSCLC.

Methods and results:  ALK status and ALK expression were evaluated in a series of 67 primary NSCLCs and their corresponding metastatic lesions using fluorescence in‐situ hybridization and immunohistochemistry. ALK rearrangement was detected in 7.5% (5/67) of the primary tumours and in 9.0% (6/67) of the metastases (P < 0.001). ALK copy number gain (CNG) was detected in 1.5% (1/67) of the primary tumours and in 35.8% (24/67) of the metastases. Whereas ALK rearrangement was detected only in adenocarcinomas, CNG was identified in various histological subtypes of NSCLC. ALK expression was detected in 11.9% (8/67) of the primary tumours and in 25.4% (17/67) of the metastatic lesions.

Conclusions:  ALK alteration and ALK expression can be acquired during metastatic progression in NSCLC, and ALK CNG is associated with ALK expression.
Population pharmacokinetics of transdermal fentanyl solution following a single dose administered prior to soft tissue and orthopedic surgery in dogs
Authors: FREISE K. J. , LINTON D. D. , NEWBOUND G. C. , TUDAN C. , CLARK T. P.
Published: June 2012

Freise, K. J., Linton, D. D., Newbound, G. C., Tudan, C., Clark, T. P. Population pharmacokinetics of transdermal fentanyl solution following a single dose administered prior to soft tissue and orthopedic surgery in dogs.J. vet. Pharmacol. Therap.35(Suppl. 2), 65–72.

A novel, long‐acting transdermal fentanyl solution (TFS) that delivers sustained plasma fentanyl concentrations following a single application for the control of postoperative pain has recently been approved for use in dogs. The pharmacokinetics (PKs) of this formulation have been evaluated in healthy laboratory dogs, but they have not been reported in a clinical population of dogs for which it is indicated. Plasma fentanyl concentrations were determined from 215 dogs following a single, small‐volume (∼50 μL/kg) dose of TFS administered 2–4 h prior to orthopedic or soft tissue surgery. A population PK model was fit, and a 1‐compartment open PK model with first‐order absorption and an absorption lag‐time best described the data. No tested clinical covariates had a significant effect on the PKs. The final model adequately described the population PKs and gave results consistent with laboratory PK studies in healthy dogs. The PKs were primarily characterized by a rapid initial increase in plasma fentanyl concentrations and a long terminal half‐life of 74.0 (95% C.I. [54.7–113]) h governed by flip‐flop kinetics for the typical subject. The plasma fentanyl concentrations were sustained over days in the range considered to be analgesic for postoperative pain in dogs.
The history of decoquinate in the control of coccidial infections in ruminants
Authors: TAYLOR M. A. , BARTRAM D. J.
Published: June 2012

Taylor, M. A., Bartram, D. J. The history of decoquinate in the control of coccidial infections in ruminants. J. vet. Pharmacol. Therap. 35, 417–427.

Decoquinate is a quinolone derivative that has been used for over 20 years in the control of coccidiosis in domestic ruminants. Decoquinate treats coccidiosis in lambs and calves and prevents coccidiosis in lambs when administered in feed at a dosage of 1 mg decoquinate/kg bodyweight (b.w.) daily for at least 28 days. It prevents coccidiosis in calves and aids in the prevention of coccidiosis in lambs when administered in calf and ewe feed, respectively, at a dosage of 0.5 mg/kg b.w. daily for at least 28 days. Decoquinate also aids in the prevention of abortions and perinatal losses owing to toxoplasmosis by medication of ewe feed at a dosage of 2 mg/kg b.w. daily, fed continuously for 14 weeks prior to lambing. Several field studies have reported reductions in cryptosporidial oocyst shedding. Decoquinate acts early in the life cycle of Eimeria on sporozoites, released from ingested oocysts, and on first‐generation meronts, arresting development and release of merozoites and thus preventing further damage to the intestines owing to the gametocyte stages. Production benefits associated with the use of decoquinate are due mainly to its action as a coccidiostat rather than any effects on diet utilization or ruminal fermentation.
Localizing the contractile deceleration point (CDP) in patients with abnormal esophageal pressure topography
Authors: Lin Z. , Pandolfino J. E. , Xiao Y. , Carlson D. , Bidari K. , Escobar G. , Kahrilas P. J.
Published: June 2012

Background  The contractile deceleration point (CDP) is an important landmark for interpreting esophageal pressure topography (EPT) plots. Previous analysis in normal subjects confirmed that the CDP could be localized using an algorithm that found the time during peristalsis at which a maximal length of the distal esophagus was contracting concurrently (tML method). This study aimed to test the tML method for localizing CDP in patients with abnormal motility.

Methods  High‐resolution manometry studies of 75 patients with normal and disordered peristalsis were analyzed. Two experts, JEP and YX, used the original tangent‐intersection method to score CDP coordinates for the first two swallows of each study. Alternative computerized algorithms tested against the expert were: (i) the tML method, (ii & iii) the intercept between the leading edge of the 30‐mmHg isobaric contour and a line 2.0 cm (or 10% of esophageal length) proximal to the esophagogastric junction (EGJ) at rest, or (iv) the ‘tML‐3 cm’ method, which added the stipulation that the CDP be within 3 cm of the EGJ.

Key Results  All tested algorithms were highly correlated with the expert. However, the tMl‐3 cm method was better in the sense that it eliminated outliers (>1 s discrepancy with the expert) that occurred with the other methods usually attributable to weak distal peristalsis.

Conclusions & Inferences  Optimal automated CDP localization was achieved in both normal and a spectrum of abnormal motility using the tML method with the added stipulation that the CDP be restricted to within the distal 3 cm of the EGJ at rest.
A phylogenetic analysis of the genera of Aphelininae (Hymenoptera: Aphelinidae), with a generic key and descriptions of new taxa
Authors: KIM JUNG‐WOOK , HERATY JOHN
Published: June 2012

The genera of Aphelininae (Aphelinidae) are reviewed on a worldwide basis. Identification keys and a phylogenetic hypothesis are presented for 16 genera, of which four are new (Mashimaron.g., Neophytisn.g., Punkaphytisn.g., Saengellan.g.) and Paraphytis is resurrected. Newly described species are Mashimaro hawksin.sp., Mashimaro lasallein.sp., Neophytis myartsevaen.sp., Neophytis munroin.sp., Punkaphytis erwinin.sp. and Punkaphytis hayatin.sp. New combinations from Aphytis include Neophytis melanosticus (Compere) and N. dealbatus (Compere), and Paraphytis acutaspidis (Rosen & DeBach), P. angusta (Compere), P. anomala (Compere), P. argenticorpa (Rosen & DeBach), P. australiensis (DeBach & Rosen), P. benassyi (Fabres), P. breviclavata (Huang), P. capillata (Howard), P. ciliata (Dodd), P. cochereaui (DeBach & Rosen), P. costalimai (Gomes), P. densiciliata (Huang), P. fabresi (DeBach & Rosen), P. haywardi (De Santis), P. hyalinipennis (Rosen & DeBach), P. maculatipennis (Dozier), P. maculata (Shafee), P. mandalayensis Rosen & DeBach, P. nigripes (Compere), P. noumeaensis (Howard), P. obscura (DeBach & Rosen), P. peculiaris (Girault), P. perplexa (Rosen & DeBach), P. transversa (Huang), P. vittata (Compere) (revived status) and P. wallumbillae (Girault). A parsimony analysis of 50 morphological characters for 54 species in 21 genera, including four outgroups (Coccophagus, Eunotiscus, Euryishomyia and Eriaphytis), resulted in three equally parsimonious trees supporting monophyly of all genera except Neophytis. Neophytis was paraphyletic to a monophyletic Aphytini but is monophyletic in unpublished molecular analyses. Three tribes are recognised (Aphelinini, Aphytini and Eutrichosomellini). The questionable inclusion of Eretmocerus (Eretmocerini) within Aphelininae is discussed.
Changes in genome content generated via segregation of non‐allelic homologs
Authors: Liu Sanzhen , Ying Kai , Yeh Cheng‐Ting , Yang Jinliang , Swanson‐Wagner Ruth , Wu Wei , Richmond Todd , Gerhardt Daniel J. , Lai Jinsheng , Springer Nathan , Nettleton Dan , Jeddeloh Jeffrey A. , Schnable Patrick S.
Published: June 2012

A careful analysis of two maize recombinant inbred lines (RILs) relative to their inbred parents revealed the presence of several hundred apparently de novo copy number variants (CNVs). These changes in genome content were validated via both PCR and whole exome‐array capture‐and‐sequencing experiments. One hundred and eighty‐five genomic regions, which overlap with 38 high‐confidence genes, exhibited apparently de novo copy number variation (CNV) in these two RILs and in many instances the same apparently de novo CNV events were observed in multiple RILs. Further analyses revealed that these recurrent apparently de novo CNVs were caused by segregation of single‐copy homologous sequences that are located in non‐allelic positions in the two parental inbred lines. F1 individuals derived from these inbred lines will be hemizygous for each of these non‐allelic homologs but RIL genotypes will contain these sequences at zero, one or two genomic loci. Hence, the segregation of non‐allelic homologs may contribute to transgressive segregation. Indeed, statistical associations between phenotypic quantitative trait loci and genomic losses were observed for two of 14 tested pairs of non‐allelic homologs.
A recurrent fibronectin glomerulopathy in a renal transplant patient: a case report
Authors: Otsuka Yasuhiro , Takeda Asami , Horike Keiji , Inaguma Daijyo , Goto Norihiko , Watarai Yoshihiko , Uchida Kazuharu , Mihatsch Michael J. , Joh Kensuke , Morozumi Kunio
Published: June 2012

Fibronectin glomerulopathy (FNG) is a rare, autosomal dominant renal disease with massive mesangial, and subendothelial fibronectin deposits. It presents proteinuria, often in the nephrotic range in the third to fourth decade, and slow progression to end‐stage renal disease. The risk of recurrent disease in renal allograft is uncertain. A Japanese female with end‐stage renal disease because of unknown origin received a renal transplant and was referred with proteinuria and mild deterioration of renal function four months after transplantation. Five allograft biopsies were underwent from one h to 12 months after the transplantation, including a biopsy 19 d after the transplantation, which revealed dense deposits suggesting fibronectin. A biopsy 134 d after the transplantation showed a feature of lobular glomerulonephritis corresponding FNG. The diagnosis was confirmed by IST4 positive and IST9 negative immunostaining together with typical fibrillary dense deposits in the mesangium and subendothelial spaces in electron microscopy. This is the first report of recurrent FNG in Japan.
The impact of fluoroquinolone resistance of Gram‐negative bacteria in respiratory secretions on the outcome of lung transplant (non‐cystic fibrosis) recipients
Authors: Shteinberg Michal , Raviv Yael , Bishara Jihad , Stein Nili , Rosengarten Dror , Bakal Ilana , Kramer Mordechai R.
Published: June 2012

Bacterial airway colonization is frequent among lung transplant recipients. These patients are often treated with antibiotics, which may lead to selection of resistant bacteria. The purpose of this study was to assess whether antibiotic treatment causes acquisition of quinolone‐resistant Gram‐negative bacteria (QR‐GNB), and the effect of such colonization on mortality and on lung rejection. We retrospectively examined data from non‐cystic fibrosis, non‐bronchiectases lung transplant recipients for antibiotic treatment, GNB in respiratory secretions, bronchiolitis obliterans syndrome (BOS), and mortality. Of 126 patients included, 86 patients had QR‐GNB, 22 had quinolone‐sensitive bacteria (QS‐GNB), and 17 had no growth. Median antibiotic exposure, defined as the fraction of days with antibiotic treatment, was 2.8% in patients without growth, 11.1% in patients with QS‐GNB (p = 0.012), and 26% in patients with QR‐GNB (p < 0.0001). Age‐adjusted mortality hazard ratio was 9.2 (95% CI 1.272–78.9) for patients with QR‐GNB compared with QS‐GNB. Age‐adjusted hazard ratios for BOS was 3.7 (95% CI 1.33–10.3) for QR‐GNB compared with QS‐GNB. We found a positive correlation between antibiotic treatment and emergence of QR‐GNB. Airway colonization with QR‐GNB was significantly associated with mortality and with BOS. Further research is needed to determine whether a change in antibiotic subscription policy is required.
Acute vascular rejection after renal transplantation and isolated v‐lesion
Authors: Shimizu Tomokazu , Tanabe Tatsu , Shirakawa Hiroki , Omoto Kazuya , Ishida Hideki , Tanabe Kazunari
Published: June 2012

Histopathological changes of acute vascular rejection (AVR) are characterized by intimal arteritis and transmural arteritis. According to the Banff 1997 classification, the quantitative criteria for intimal arteritis (v score) are classified: v0, v1, v2, and v3. According to Banff ‘09 classification, AVR may fall into one of four categories: acute T cell‐mediated rejection (ATMR) Type IIA, ATMR Type IIB, ATMR Type III, and acute antibody‐mediated rejection (AAMR) Type III.

Both cellular and humoral immunity play roles in vascular rejection, and in some cases, AVR may be provoked by anti‐donor antibodies. Anti‐rejection therapies were effective in most of the v1 cases but were less effective in the v2 cases and were ineffective in the v3 cases. Some reports have indicated that the prognosis of grafts exhibiting AVR is poor, but in our series, the outcome of AVR was relatively good using recent immunosuppressive protocols.

A definition for “isolated v‐lesion” was originally characterized by arteritis with minimal interstitial inflammation and tubulitis. The 11th Banff conference was concluded that “isolated v1‐lesions” comprised two types, T cell‐mediated rejection and injury, and did not have any independent prognostic significance. However, we speculate that “isolated v‐lesion” might be regarded as AAMR and ATMR.
Tension‐free vaginal tape procedure without preoperative urodynamic examination: Long‐term outcome
Authors: Heinonen Pia , Ala‐Nissilä Seija , Kiilholma Pentti , Laurikainen Eija
Published: June 2012

Objectives:  To evaluate the long‐term outcome of the tension‐free vaginal tape procedure.

Methods:  A total of 191 patients were operated on with tension‐free vaginal tape between January 1998 and May 2000. Of these, 127 (66%) had stress urinary incontinence, 64 (34%) had mixed urinary incontinence and 39 (20%) had recurrent incontinence. A total of 34 (18%) patients had had concomitant surgery. The diagnosis of incontinence was based on a history of leakage during stress and physical examination with a supine stress test in all patients. Tension‐free vaginal tape was carried out under local (82%) or spinal (18%) anesthesia. After a mean of 10.5 years follow up, the assessment included a gynecological examination and a supine stress test. Subjective outcome was evaluated with Urinary Incontinence Severity Score, Detrusor Instability Score, visual analog scale, European quality of life‐five dimensions, European quality of life – visual analog scale and short versions of Incontinence Impact Questionnaire‐7 and Urogenital Distress Inventory‐6. Objective cure was defined as a negative stress test and an absence of reoperation for incontinence during the follow up.

Results:  A total of 138 (72%) of 191 patients were evaluated. Patients with minimally invasive surgery before operation had significantly higher scores in Urinary Incontinence Severity Score, Detrusor Instability Score, Incontinence Impact Questionnaire‐7 and Urogenital Distress Inventory‐6 at follow up than the patients with stress urinary incontinence (P < 0.01). Recurrent incontinence and concomitant surgery did not affect the long‐term outcome. Three patients (2.3%) had late‐onset adverse events. The objective and subjective cure rates were 90% and 78%, respectively.

Conclusions:  The tension‐free vaginal tape procedure is effective and safe even after 10 years. The objective cure rate is high, but the subjective outcome is significantly lower in mixed urinary incontinence patients compared with patients with pure stress urinary incontinence. Recurrent stress urinary incontinence does not affect the outcome, and tape‐related problems are rare.
Endoscopy after radiology: Two‐step combined therapy for biliary stricture after Roux‐en‐Y hepaticojejunostomy
Authors: Curcio Gabriele , Traina Mario , Miraglia Roberto , Tarantino Ilaria , Barresi Luca , Granata Antonino , Luca Angelo , Gridelli Bruno
Published: June 2012

Benign postoperative anastomotic strictures after hepaticojejunostomy are difficult to manage. Before interventional techniques were developed, surgical intervention was the only option for treatment. A 28‐year‐old man underwent Whipple procedure with Roux‐en‐Y hepaticojejunostomy for abdominal trauma. Two years later, a late anastomotic biliary stricture was diagnosed. A percutaneous cholangiography showed a severe stricture in the hepaticojejunostomy. Because of the severity and length of the stricture, and the failure of repeated percutaneous balloon‐dilations, we percutaneously placed a self‐expandable metal stent, a nitinol polytetrafluoroethylene fully covered flared‐type stent, 3 cm in length, with 10 mm of diameter. The patient was soon discharged home in good general condition that remained stable in the 6 months of follow up. To remove the biliary stent, we carried out single‐balloon enteroscopy. The stent was captured with a standard polypectomy snare. To avoid injury to the mucosa, the stent was removed through the overtube, which remained in situ. Cholangiogram showed a normal biliary tree, with resolution of the anastomotic stenosis. The patient remained stable throughout the 8 months of follow up, and required no further biliary procedures. In cases of failure of standard procedures, this new two‐step, combined percutaneous and endoscopic approach can be useful and feasible, avoiding surgery‐related morbidity and mortality. However, the fact that these procedures should be carried out only by highly experienced endoscopists and interventional radiologists familiar with these specialized procedures cannot be overstressed.
A case of Ménétrier's disease without Helicobacter pylori infection
Authors: Endo Takao , Arimura Yoshiaki , Adachi Yasushi , Mita Hiroaki , Yamashita Kentaro , Yamamoto Hiroyuki , Shinomura Yasuhisa , Ishii Yoshifumi
Published: June 2012

Ménétrier's disease (MD) is a rare, acquired, premalignant disorder of the stomach characterized by enlarged gastric folds with foveolar hyperplasia, the phenotype of antralization of gastric glands, hypochlorhydria and hypoproteinemia. The etiology of MD is unknown, but both increased signaling by transforming growth factor‐α and infection with Helicobacter pylori (H. pylori) have been implicated. Here, a case involving 70‐year‐old man who lost weight after developing anorexia and diarrhea is reported. He was diagnosed as MD without H. pylori infection, and in spite of intensive care, he died 40 days after admission. An autopsy confirmed MD. Immunohistochemistry revealed overexpression of transforming growth factor‐α in the foveolar region of the gastric mucosa. The autopsy also distinguished this H. pylori‐negative MD from hyperplastic polyp of the stomach, which is important in clarifying the entity of H. pylori‐negative MD.
Kelp Diagrams: Point Set Membership Visualization
Authors: Dinkla Kasper , van Kreveld Marc J. , Speckmann Bettina , Westenberg Michel A.
Published: June 2012

We present Kelp Diagrams, a novel method to depict set relations over points, i.e., elements with predefined positions. Our method creates schematic drawings and has been designed to take aesthetic quality, efficiency, and effectiveness into account. This is achieved by a routing algorithm, which links elements that are part of the same set by constructing minimum cost paths over a tangent visibility graph. There are two styles of Kelp Diagrams to depict overlapping sets, a nested and a striped style, each with its own strengths and weaknesses. We compare Kelp Diagrams with two existing methods and show that our approach provides a more consistent and clear depiction of both element locations and their set relations.
Reliable Adaptive Modelling of Vascular Structures with Non‐Circular Cross‐Sections
Authors: Kretschmer Jan , Beck Thomas , Tietjen Christian , Preim Bernhard , Stamminger Marc
Published: June 2012

Accurate visualizations of complex vascular structures are essential for medical applications, such as diagnosis, therapy planning and medical education. Vascular trees are usually described using centerlines, since they capture both the topology and the geometry of the vasculature in an intuitive manner. State‐of‐the‐art vessel segmentation algorithms deliver vascular outlines as free‐form contours along the centerline, since this allows capturing anatomical pathologies. However, existing methods for generating surface representations from centerlines can only cope with circular outlines. We present a novel model‐based technique that is capable of generating intersection‐free surfaces from centerlines with complex outlines. Vascular segments are described by local signed distance functions and combined using Boolean operations. An octree‐based surface generation strategy automatically computes watertight, scale‐adaptive meshes with a controllable quality. In contrast to other approaches, our method generates a reliable representation that guarantees to capture all vessels regardless of their size.
Visualization of 4D Blood‐Flow Fields by Spatiotemporal Hierarchical Clustering
Authors: van Pelt R. F. P. , Jacobs S. S. A. M. , ter Haar Romeny B. M. , Vilanova A.
Published: June 2012

Advancements in the acquisition and modeling of flow fields result in unsteady volumetric flow fields of unprecedented quality. An important example is found in the analysis of unsteady blood‐flow data. Preclinical research strives for a better understanding of correlations between the hemodynamics and the progression of cardiovascular diseases. Modern‐day computer models and MRI acquisition provide time‐resolved volumetric blood‐flow velocity fields. Unfortunately, these fields often remain unexplored, as high‐dimensional data are difficult to conceive. We present a spatiotemporal, i.e., four‐dimensional, hierarchical clustering, yielding a sparse representation of the velocity data. The clustering results underpin an illustrative visualization approach, facilitating visual analysis. The hierarchy allows an intuitive level‐of‐detail selection, largely retaining important flow patterns. The clustering employs dissimilarity measures to construct the hierarchy. We have adapted two existing measures for steady vector fields for use in the spacetime domain. Because of the inherent computational complexity of the multidimensional clustering, we introduce a coarse hierarchical clustering approach, which closely approximates the full hierarchy generation, and considerably improves the performance. The resulting clusters are visualized by representative patharrows, in combination with an illustrative anatomical context. We present various seeding approaches and visualization styles, providing sparse overviews of the unsteady behavior of volumetric flow fields.
Automatic Stream Surface Seeding: A Feature Centered Approach
Authors: Edmunds M. , Laramee R.S. , Malki R. , Masters I. , Croft T.N. , Chen G. , Zhang E.
Published: June 2012

The ability to capture and visualize information within the flow poses challenges for visualizing 3D flow fields. Stream surfaces are one of many useful integration based techniques for visualizing 3D flow. However seeding integral surfaces can be challenging. Previous research generally focuses on manual placement of stream surfaces. Little attention has been given to the problem of automatic stream surface seeding. This paper introduces a novel automatic stream surface seeding strategy based on vector field clustering. It is important that the user can define and target particular characteristics of the flow. Our framework provides this ability. The user is able to specify different vector clustering parameters enabling a range of abstraction for the density and placement of seeding curves and their associated stream surfaces. We demonstrate the effectiveness of this automatic stream surface approach on a range of flow simulations and incorporate illustrative visualization techniques. Domain expert evaluation of the results provides valuable insight into the users requirements and effectiveness of our approach.
Visualization of Advection‐Diffusion in Unsteady Fluid Flow
Authors: Karch Grzegorz Karol , Sadlo Filip , Weiskopf Daniel , Munz Claus‐Dieter , Ertl Thomas
Published: June 2012

Advection has been the standard transport mechanism in flow visualization. Diffusion, in contrast, has not been considered important in visual flow field analysis so far, although it is inherent to many physical processes. We present a novel technique that allows for interactive 3D visualization of both advection and diffusion in unsteady fluid flow. We extend texture‐based flow visualization, which is advection‐oriented, by diffusion. Our finite volume approach based on WENO (weighted essentially non‐oscillatory) reconstruction is well parallelizable and features low numerical diffusion at interactive rates. Our scheme contributes to three different applications: (a) high‐quality dye advection at low numerical diffusion, (b) physically‐based dye advection accounting for diffusivity of virtual media, and (c) visualization of advection‐diffusion fluxes in physical media where the velocity field is accompanied by a concentration field. Interactive rendering of the virtual dye is accomplished by ray casting. We apply our GPU implementation to CFD examples of thermal convection and evaporation phenomena.
Semantic Wordification of Document Collections
Authors: Paulovich Fernando V. , Toledo Franklina M. B. , Telles Guilherme P. , Minghim Rosane , Nonato Luis Gustavo
Published: June 2012

Word clouds have become one of the most widely accepted visual resources for document analysis and visualization, motivating the development of several methods for building layouts of keywords extracted from textual data. Existing methods are effective to demonstrate content, but are not capable of preserving semantic relationships among keywords while still linking the word cloud to the underlying document groups that generated them. Such representation is highly desirable for exploratory analysis of document collections. In this paper we present a novel approach to build document clouds, named ProjCloud that aim at solving both semantical layouts and linking with document sets. ProjCloud generates a semantically consistent layout from a set of documents. Through a multidimensional projection, it is possible to visualize the neighborhood relationship between highly related documents and their corresponding word clouds simultaneously. Additionally, we propose a new algorithm for building word clouds inside polygons, which employs spectral sorting to maintain the semantic relationship among words. The effectiveness and flexibility of our methodology is confirmed when comparisons are made to existing methods. The technique automatically constructs projection based layouts the user may choose to examine in the form of the point clouds or corresponding word clouds, allowing a high degree of control over the exploratory process.
Perception of Animated Node‐Link Diagrams for Dynamic Graphs
Authors: Ghani S. , Elmqvist N. , Yi J. S.
Published: June 2012

Effective visualization of dynamic graphs remains an open research topic, and many state‐of‐the‐art tools use animated node‐link diagrams for this purpose. Despite its intuitiveness, the effectiveness of animation in node‐link diagrams has been questioned, and several empirical studies have shown that animation is not necessarily superior to static visualizations. However, the exact mechanics of perceiving animated node‐link diagrams are still unclear. In this paper, we study the impact of different dynamic graph metrics on user perception of the animation. After deriving candidate visual graph metrics, we perform an exploratory user study where participants are asked to reconstruct the event sequence in animated node‐link diagrams. Based on these findings, we conduct a second user study where we investigate the most important visual metrics in depth. Our findings show that node speed and target separation are prominent visual metrics to predict the performance of event sequencing tasks.
Visualizing Motion Data in Virtual Reality: Understanding the Roles of Animation, Interaction, and Static Presentation
Authors: Coffey D. , Korsakov F. , Ewert M. , Hagh‐Shenas H. , Thorson L. , Ellingson A. , Nuckley D. , Keefe D.F
Published: June 2012

We present a study of interactive virtual reality visualizations of scientific motions as found in biomechanics experiments. Our approach is threefold. First, we define a taxonomy of motion visualizations organized by the method (animation, interaction, or static presentation) used to depict both the spatial and temporal dimensions of the data. Second, we design and implement a set of eight example visualizations suggested by the taxonomy and evaluate their utility in a quantitative user study. Third, together with biomechanics collaborators, we conduct a qualitative evaluation of the eight example visualizations applied to a current study of human spinal kinematics. Results suggest that visualizations in this style that use interactive control for the time dimension of the data are preferable to others. Within this category, quantitative results support the utility of both animated and interactive depictions for space; however, qualitative feedback suggest that animated depictions for space should be avoided in biomechanics applications.
MatchPad: Interactive Glyph‐Based Visualization for Real‐Time Sports Performance Analysis
Authors: Legg P. A. , Chung D. H. S. , Parry M. L. , Jones M. W. , Long R. , Griffiths I. W. , Chen M.
Published: June 2012

Today real‐time sports performance analysis is a crucial aspect of matches in many major sports. For example, in soccer and rugby, team analysts may annotate videos during the matches by tagging specific actions and events, which typically result in some summary statistics and a large spreadsheet of recorded actions and events. To a coach, the summary statistics (e.g., the percentage of ball possession) lacks sufficient details, while reading the spreadsheet is time‐consuming and making decisions based on the spreadsheet in real‐time is thereby impossible. In this paper, we present a visualization solution to the current problem in real‐time sports performance analysis. We adopt a glyph‐based visual design to enable coaching staff and analysts to visualize actions and events “at a glance”. We discuss the relative merits of metaphoric glyphs in comparison with other types of glyph designs in this particular application. We describe an algorithm for managing the glyph layout at different spatial scales in interactive visualization. We demonstrate the use of this technical approach through its application in rugby, for which we delivered the visualization software,MatchPad, on a tablet computer. The MatchPad was used by the Welsh Rugby Union during the Rugby World Cup 2011. It successfully helped coaching staff and team analysts to examine actions and events in detail whilst maintaining a clear overview of the match, and assisted in their decision making during the matches. It also allows coaches to convey crucial information back to the players in a visually‐engaging manner to help improve their performance.
Religion and HIV diagnosis among Africans living in London
Authors: Fakoya I , Johnson AM , Fenton KA , Anderson J , Nwokolo N , Sullivan AK , Munday P , Burns FM
Published: June 2012

Objectives

The aim of the paper was to describe the association of religion with HIV outcomes in newly diagnosed Africans living in London.

Methods

A survey of newly diagnosed HIV‐positive Africans attending 15 HIV treatment centres across London was carried out between April 2004 and February 2006. Confidential self‐completed questionnaires were used, linked to clinical records. Bivariate analyses were conducted to ascertain whether religious beliefs were associated with late diagnosis, antiretroviral therapy, and immunological and virological outcome 6 months post diagnosis.

Results

A total of 246 Black Africans were eligible and included in the analysis: 62.6% were women, and the median age was 34 years. The median CD4 count at diagnosis was 194 cells/μL (range 0–1334 cells/μL) and 75.6% presented late, as defined as a CD4 count < 350 cells/μL. Most participants were religious: non‐Roman Catholic Christians (55.7%), Roman Catholics (35.2%) and Muslims (6.1%). Only 1.2% stated that they did not have a religion. Participants who attended religious services at least monthly were more likely to believe that ‘faith alone can cure HIV‘ than those who attended less frequently (37.7% vs. 15.0%; P = 0.002). A small proportion (5.2%) believed that taking antiretroviral therapy implied a lack of faith in God. Bivariate analysis found no relationship between religiousness (as measured using frequency of attendance at religious services and religious attitudes or beliefs) and late diagnosis, changes in CD4 count/viral load 6 months post diagnosis, or initiation of antiretroviral therapy.

Conclusions

Strong religious beliefs about faith and healing are unlikely to act as a barrier to accessing HIV testing or antiretroviral treatment for Black Africans living in London.