bluuebunny/crossref_metadata_2025 huggingface dataset:
A simple approach of three-isocenter IMRT planning for craniospinal irradiation
Authors: Wang Zheng , Jiang Wei , Feng Yuanming , Guo Yang , Cong Zheng , Song Bin , Guo Yu
Published: September 2013

Purpose

To develop a new IMRT technique to simplify the process and improve efficiency in radiotherapy treatment planning for craniospinal irradiation (CSI) treatment.

Methods

Image data of 9 patients who received CSI treatment in 2012 were used, the prescription was 36Gy in 20 fractions. Two treatment plans were created for each patient, one was with the new technique called three-isocenter overlap-junction (TIOJ) IMRT and the other was with the three-isocenter jagged-junction (TIJJ) IMRT technique. The comparative study was conducted using the parameters of heterogeneity index (HI), conformity index (CI), and doses to the organs at risk (OARs).

Results

Comparing the TIOJ IMRT plans with the TIJJ IMRT plans, the average homogeneity index is 0.071 ± 0.003 and 0.077 ± 0.002, respectively, and the averaged conformity number is 0.80 ± 0.012 and 0.80 ± 0.009, respectively. There are no significant differences (p > 0.05). Both plans provide satisfactory sparing for the OARs.

Conclusions

The TIOJ IMRT technique for CSI treatment planning can create similar plans as with the TIJJ IMRT technique, but the new technique greatly simplifies the steps required to manually set field widths and boundaries and improved efficiency.
Investigation of the biomechanical effect of variable stiffness shoe on external knee adduction moment in various dynamic exercises
Authors: Teoh Jee Chin , Low Jin Huat , Lim Ying Bena , Shim Victor Phyau‐Wui , Park Jaeyoung , Park Seung‐Bum , Park Sang Jun , Lee Taeyong
Published: September 2013

Background

The growing ageing population and high prevalence of knee osteoarthritis (OA) in athletes across nations have created a strong demand for improved non‐invasive therapeutic alternatives for knee OA. The aim of this study is to investigate the effect of the variable stiffness shoe (VSS), a new non‐invasive therapeutic approach, on external knee adduction moment (EKAM) in various dynamic exercises. EKAM is believed to have positive correlation with the progression and development of knee OA.

Methods

Thirty young participants (16 male and 14 female; age 22.6 ± 1.9 years) from National University of Singapore were enrolled in this study. The tested activities were walking, running, drop‐landing, and lateral hopping. All the dynamic exercises were recorded simultaneously by the 8‐camera VICON Motion Systems (Oxford Metric, UK) with a sampling rate of 100 Hz.

Results

The results showed that the EKAM was reduced in all the dynamic exercises with the use of VSS. The VSS produced significant reductions in the peak EKAM during walking (4.97%, p = 0.039), running (11.15%, p = 0.011), drop‐landing (11.18%, p = 0.038) and lateral hopping (17.34%, p = 0.023) as compared to the control shoe.

Conclusions

The reduction of EKAM with the use of VSS in various dynamic exercises demonstrates its potential in delaying the onset and the progression of knee OA in early stage of knee OA patients.
Opportunities and challenges for gut microbiome studies in the Indian population
Authors: Shetty Sudarshan Anand , Marathe Nachiket Prakash , Shouche Yogesh S
Published: September 2013

The gut microbiome is a complex ecosystem that affects the development, immunological responses and nutritional status of the host. Efforts are being made to unravel the complex interaction between the gut microbiome and host to have a greater understanding about its role in human health. Colonization of the gut by microbes begins at birth, but the succession and composition of the microbial community depends on a number of factors including, but not limited to, the age, diet, genetic composition, gender, geographic location, and health status of an individual. Therefore, inclusion of diverse human subjects in the study of the gut microbiome is indispensable. However, conducting such studies in India presents unique opportunities and challenges. The vast diversity in human genetic composition, dietary habits, and geographic distribution that exists in the Indian population adds to the complexity in understanding the gut microbiome. Gut microbiome-related studies from other parts of the world have reported a possible association of diseases such as obesity and diabetes with the human gut microbiome. In contrast, an in-depth assessment of risk factors associated with altered gut microbiome in such diseases in the Indian population is lacking. Studies including the Indian population may give insights into the association of the gut microbiome with various factors and diseases that may not be possible from studies on western populations. This review briefly discusses the significance of the gut microbiome on human health and the present status of gut microbiome studies in the Indian population. In addition, this review will highlight the unique opportunities and challenges for gut microbiome studies in the Indian population.
Use of Early Tumor Shrinkage to Predict Long-Term Outcome in Metastatic Colorectal Cancer Treated With Cetuximab
Authors: Piessevaux Hubert , Buyse Marc , Schlichting Michael , Van Cutsem Eric , Bokemeyer Carsten , Heeger Steffen , Tejpar Sabine
Published: September 2013

Purpose

Early tumor shrinkage (ETS) is associated with long-term outcome in patients with chemorefractory metastatic colorectal cancer (mCRC) receiving cetuximab. This association was investigated in the first-line setting in the randomized CRYSTAL and OPUS mCRC trials, after controlling for KRAS tumor mutation status.

Methods

Radiologic assessments at week 8 were used to calculate the relative change in the sum of the longest diameters of the target lesions. Time-dependent receiver operating characteristics provided Cτ-indices (time-dependent c-index). Cox regression models and subpopulation treatment effect pattern plot analysis investigated associations between ETS (radiologic tumor size decrease at week 8) and survival and progression-free survival (PFS).

Results

In both trials, in patients with KRAS wild-type mCRC, Cτ values for PFS and survival were higher (P < .001) in those receiving chemotherapy plus cetuximab versus chemotherapy alone, indicating a stronger predictive value of ETS for long-term outcome in these patients. In the CRYSTAL and OPUS trials, respectively, the cutoff value of ETS ≥ 20% (v < 20%) identified patients with KRAS wild-type mCRC receiving chemotherapy plus cetuximab with longer PFS (medians 14.1 v 7.3 months, hazard ratio [HR] = 0.32; P < .001, and medians 11.9 v 5.7 months, HR = 0.22; P < .001) and survival (medians 30.0 v 18.6 months, HR = 0.53; P < .001 and medians 26.0 v 15.7 months, HR = 0.43; P = .006).

Conclusion

ETS was significantly associated with long-term outcome in patients with KRAS wild-type mCRC treated first-line with chemotherapy plus cetuximab. Validation in prospective trials is required to assess the value of this on-treatment marker in the clinical decision-making process.
Denosumab and Bone Metastasis–Free Survival in Men With Nonmetastatic Castration-Resistant Prostate Cancer: Exploratory Analyses by Baseline Prostate-Specific Antigen Doubling Time
Authors: Smith Matthew R. , Saad Fred , Oudard Stephane , Shore Neal , Fizazi Karim , Sieber Paul , Tombal Bertrand , Damiao Ronaldo , Marx Gavin , Miller Kurt , Van Veldhuizen Peter , Morote Juan , Ye Zhishen , Dansey Roger , Goessl Carsten
Published: September 2013

Purpose

Denosumab, an anti–RANK ligand monoclonal antibody, significantly increases bone metastasis–free survival (BMFS; hazard ratio [HR], 0.85; P = .028) and delays time to first bone metastasis in men with nonmetastatic castration-resistant prostate cancer (CRPC) and baseline prostate-specific antigen (PSA) ≥ 8.0 ng/mL and/or PSA doubling time (PSADT) ≤ 10.0 months. To identify men at greatest risk for bone metastasis or death, we evaluated relationships between PSA and PSADT with BMFS in the placebo group and the efficacy and safety of denosumab in men with PSADT ≤ 10, ≤ 6, and ≤ 4 months.

Patients and Methods

A total of 1,432 men with nonmetastatic CRPC were randomly assigned 1:1 to monthly subcutaneous denosumab 120 mg or placebo. Enrollment began February 2006; primary analysis cutoff was July 2010, when approximately 660 men were anticipated to have developed bone metastases or died.

Results

In the placebo group, shorter BMFS was observed as PSADT decreased below 8 months. In analyses by shorter baseline PSADT, denosumab consistently increased BMFS by a median of 6.0, 7.2, and 7.5 months among men with PSADT ≤ 10 (HR, 0.84; P = .042), ≤ 6 (HR, 0.77; P = .006), and ≤ 4 months (HR, 0.71; P = .004), respectively. Denosumab also consistently increased time to bone metastasis by PSADT subset. No difference in survival was observed between treatment groups for the overall study population or PSADT subsets.

Conclusion

Patients with shorter PSADT are at greater risk for bone metastasis or death. Denosumab consistently improves BMFS in men with shorter PSADT and seems to have the greatest treatment effects in men at high risk for progression.
Barriers Against Psychosocial Communication: Oncologists' Perceptions
Authors: Fagerlind Hanna , Kettis Åsa , Glimelius Bengt , Ring Lena
Published: September 2013

Purpose

To explore oncologists' psychosocial attitudes and beliefs and their perceptions regarding barriers against psychosocial communication.

Methods

A questionnaire was distributed to oncologists in Sweden (n = 537). Questions covered demography, the Physician Psychosocial Beliefs Scale (PPBS), and barriers against psychosocial communication. Stepwise multiple regression was used to determine what factors contribute the most to the PPBS score and the total number of barriers and barriers affecting clinical practice, respectively. Spearman rank-order correlation was used to determine correlation between PPBS score and number of barriers.

Results

Questionnaire response rate was 64%. Mean PPBS value was 85.5 (range, 49 to 123; SD, 13.0). Most oncologists (93%) perceived one or more barriers in communicating psychosocial aspects with patients. On average, five different communication barriers were perceived, of which most were perceived to affect clinical practice. These barriers included insufficient consultation time, lack of resources for taking care of problems discovered, and lack of methods to evaluate patients' psychosocial health in clinical practice. There was a positive correlation (rs = 0.490; P < .001) between the PPBS score and the number of perceived barriers (ie, less psychosocially oriented oncologists perceived more barriers). Oncologists with supplementary education with a psychosocial focus perceived fewer barriers/barriers affecting clinical practice (P < .001 and P = .001, respectively) and were more psychosocially oriented (P = .001).

Conclusion

Oncologists perceive many different barriers affecting psychosocial communication in clinical practice. Interventions aiming to improve psychosocial communication must therefore be multifaceted and individualized to clinics and individual oncologists. It is important to minimize barriers to facilitate optimal care and treatment of patients with cancer.
Phase II Study of Alisertib, a Selective Aurora A Kinase Inhibitor, in Relapsed and Refractory Aggressive B- and T-Cell Non-Hodgkin Lymphomas
Authors: Friedberg Jonathan W. , Mahadevan Daruka , Cebula Erin , Persky Daniel , Lossos Izidore , Agarwal Amit B. , Jung JungAh , Burack Richard , Zhou Xiaofei , Leonard E. Jane , Fingert Howard , Danaee Hadi , Bernstein Steven H.
Published: September 2013

Purpose

Aurora A kinase (AAK) is overexpressed in aggressive lymphomas and can correlate with more histologically aggressive forms of disease. We therefore designed a phase II study of alisertib, a selective AAK inhibitor, in patients with relapsed and refractory aggressive non-Hodgkin lymphomas.

Patients and Methods

Patients age ≥ 18 years were eligible if they had relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle-cell lymphoma (MCL), transformed follicular lymphoma, Burkitt's lymphoma, or noncutaneous T-cell lymphoma. Alisertib was administered orally at 50 mg twice daily for 7 days in 21-day cycles.

Results

We enrolled 48 patients. Histologies included DLBCL (n = 21), MCL (n = 13), peripheral T-cell lymphoma (n = 8), transformed follicular lymphoma (n = 5), and Burkitt's (n = 1). Most common grade 3 to 4 adverse events were neutropenia (63%), leukopenia (54%), anemia (35%), thrombocytopenia (33%), stomatitis (15%), febrile neutropenia (13%), and fatigue (6%). Four deaths during the study were attributed to progressive non-Hodgkin lymphoma (n = 2), treatment-related sepsis (n = 1), and unknown cause (n = 1). The overall response rate was 27%, including responses in three of 21 patients with DLBCL, three of 13 with MCL, one of one with Burkitt's lymphoma, two of five with transformed follicular lymphoma, and four of eight with noncutaneous T-cell lymphoma. The alisertib steady-state trough concentration (n = 25) revealed the expected pharmacokinetic variability, with a trend for higher incidence of adverse event–related dose reductions at higher trough concentrations. Analysis for AAK gene amplification and total AAK protein revealed no differences between histologies or correlation with clinical response.

Conclusion

The novel AAK inhibitor alisertib seems clinically active in both B- and T-cell aggressive lymphomas. On the basis of these results, confirmatory single-agent and combination studies have been initiated.
Breast-Conserving Treatment With or Without Radiotherapy in Ductal Carcinoma In Situ: 15-Year Recurrence Rates and Outcome After a Recurrence, From the EORTC 10853 Randomized Phase III Trial
Authors: Donker Mila , Litière Saskia , Werutsky Gustavo , Julien Jean-Pierre , Fentiman Ian S. , Agresti Roberto , Rouanet Philippe , de Lara Christine Tunon , Bartelink Harry , Duez Nicole , Rutgers Emiel J.T. , Bijker Nina
Published: September 2013

Purpose

Adjuvant radiotherapy (RT) after a local excision (LE) for ductal carcinoma in situ (DCIS) aims at reduction of the incidence of a local recurrence (LR). We analyzed the long-term risk on developing LR and its impact on survival after local treatment for DCIS.

Patients and Methods

Between 1986 and 1996, 1,010 women with complete LE of DCIS less than 5 cm were randomly assigned to no further treatment (LE group, n = 503) or RT (LE+RT group, n = 507). The median follow-up time was 15.8 years.

Results

Radiotherapy reduced the risk of any LR by 48% (hazard ratio [HR], 0.52; 95% CI, 0.40 to 0.68; P < .001). The 15-year LR-free rate was 69% in the LE group, which was increased to 82% in the LE+RT group. The 15-year invasive LR-free rate was 84% in the LE group and 90% in the LE+RT group (HR, 0.61; 95% CI, 0.42 to 0.87). The differences in LR in both arms did not lead to differences in breast cancer–specific survival (BCSS; HR, 1.07; 95% CI, 0.60 to 1.91) or overall survival (OS; HR, 1.02; 95% CI, 0.71 to 1.44). Patients with invasive LR had a significantly worse BCSS (HR, 17.66; 95% CI, 8.86 to 35.18) and OS (HR, 5.17; 95% CI, 3.09 to 8.66) compared with those who did not experience recurrence. A lower overall salvage mastectomy rate after LR was observed in the LE+RT group than in the LE group (13% v 19%, respectively).

Conclusion

At 15 years, almost one in three nonirradiated women developed an LR after LE for DCIS. RT reduced this risk by a factor of 2. Although women who developed an invasive recurrence had worse survival, the long-term prognosis was good and independent of the given treatment.
Lymphoma Occurring During Pregnancy: Antenatal Therapy, Complications, and Maternal Survival in a Multicenter Analysis
Authors: Evens Andrew M. , Advani Ranjana , Press Oliver W. , Lossos Izidore S. , Vose Julie M. , Hernandez-Ilizaliturri Francisco J. , Robinson Barrett K. , Otis Stavroula , Nadav Dagan Liat , Abdallah Ramsey , Kroll-Desrosiers Aimee , Yarber Jessica L. , Sandoval Jose , Foyil Kelley , Parker Linda M. , Gordon Leo I. , Blum Kristie A. , Flowers Christopher R. , Leonard John P. , Habermann Thomas M. , Bartlett Nancy L.
Published: September 2013

Purpose

Lymphoma is the fourth most frequent cancer in pregnancy; however, current clinical practice is based largely on small series and case reports.

Patients and Methods

In a multicenter retrospective analysis, we examined treatment, complications, and outcomes for Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) occurring during pregnancy.

Results

Among 90 patients (NHL, n = 50; HL, n = 40), median age was 30 years (range, 18 to 44 years) and median diagnosis occurred at 24 weeks gestation. Of patients with NHL, 52% had advanced-stage versus 25% of patients with HL (P = .01). Pregnancy was terminated in six patients. Among the other 84 patients, 28 (33%) had therapy deferred to postpartum; these patients were diagnosed at a median 30 weeks gestation. This compared with 56 patients (67%) who received antenatal therapy with median lymphoma diagnosis at 21 weeks (P < .001); 89% of these patients received combination chemotherapy. The most common preterm complication was induction of labor (33%). Gestation went to full term in 56% of patients with delivery occurring at a median of 37 weeks. There were no differences in maternal complications, perinatal events, or median infant birth weight based on deferred versus antenatal therapy. At 41 months, 3-year progression-free survival (PFS) and overall survival (OS) for NHL were 53% and 82%, respectively, and 85% and 97%, respectively, for HL. On univariate analysis for NHL, radiotherapy predicted inferior PFS, and increased lactate dehydrogenase and poor Eastern Cooperative Oncology Group performance status (ECOG PS) portended worse OS. For HL patients, nulliparous status and “B” symptoms predicted inferior PFS.

Conclusion

Standard (non-antimetabolite) combination chemotherapy administered past the first trimester, as early as 13 weeks gestation, was associated with few complications and expected maternal survival with lymphoma occurring during pregnancy.
Solid Tumors After Chemotherapy or Surgery for Testicular Nonseminoma: A Population-Based Study
Authors: Fung Chunkit , Fossa Sophie D. , Milano Michael T. , Oldenburg Jan , Travis Lois B.
Published: September 2013

Purpose

Increased risks of solid tumors after older radiotherapy strategies for testicular cancer (TC) are well established. Few population-based studies, however, focus on solid cancer risk among survivors of TC managed with nonradiotherapy approaches. We quantified the site-specific risk of solid cancers among testicular nonseminoma patients treated in the modern era of cisplatin-based chemotherapy, without radiotherapy.

Patients and Methods

Standardized incidence ratios (SIRs) for solid tumors were calculated for 12,691 patients with testicular nonseminoma reported to the population-based Surveillance, Epidemiology, and End Results program (1980 to 2008) and treated initially with either chemotherapy (n = 6,013) or surgery (n = 6,678) without radiotherapy. Patients accrued 116,073 person-years of follow-up.

Results

Two hundred ten second solid cancers were observed. No increased risk followed surgery alone (SIR, 0.93; 95% CI, 0.76 to 1.14; n = 99 solid cancers), whereas significantly increased 40% excesses (SIR, 1.43; 95% CI, 1.18 to 1.73; n = 111 solid cancers) occurred after chemotherapy. Increased risks of solid cancers after chemotherapy were observed in most follow-up periods (median latency, 12.5 years), including more than 20 years after treatment (SIR, 1.54; 95% CI, 0.96 to 2.33); significantly increased three- to seven-fold risks occurred for cancers of the kidney (SIR, 3.37; 95% CI, 1.79 to 5.77), thyroid (SIR, 4.40; 95% CI, 2.19 to 7.88), and soft tissue (SIR, 7.49; 95% CI, 3.59 to 13.78).

Conclusion

To our knowledge, this is the first large population-based series reporting significantly increased risks of solid cancers among patients with testicular nonseminoma treated in the modern era of cisplatin-based chemotherapy. Subsequent analytic studies should focus on the evaluation of dose-response relationships, types of solid cancers, latency patterns, and interactions with other possible factors, including genetic susceptibility.
Assessing Patient-Centered Communication in Cancer Care: Stakeholder Perspectives
Authors: Mazor Kathleen M. , Gaglio Bridget , Nekhlyudov Larissa , Alexander Gwen L. , Stark Azadeh , Hornbrook Mark C. , Walsh Kathleen , Boggs Jennifer , Lemay Celeste A. , Firneno Cassandra , Biggins Colleen , Blosky Mary Ann , Arora Neeraj K.
Published: September 2013

Patient reports of their communication experiences during cancer care could increase understanding of the communication process, stimulate improvements, inform interventions, and provide a basis for evaluating changes in communication practices.
Plantation Modernity:Gone with the Windand Irish-Southern Culture
Authors: Clukey Amy
Published: September 2013

The last ten years have seen a reexamination of Margaret Mitchell’s depictions of Irish identity. While these readings tell us a great deal about how Mitchell depicts Irish immigration to the region, colonial history shows that the connections between Ireland and the American South go beyond the well-documented transatlantic mobility of the Irish diaspora. As such, a comparative perspective is necessary to fully understand that the novel’s famous blending of Irish ethnicity and Southern history is part of a larger transnational phenomenon; although Gone with the Wind seems to be a defiantly local literary expression, it is in fact a product of the global socioeconomic and cultural matrix of what Clukey calls plantation modernity. In this essay, Clukey seeks to move past cultural similarities between Ireland and the South in order to establish the Anglo-Irish big house and the American plantation as contiguous colonial sites—and the big-house novel and plantation fiction as contiguous literary traditions. Plantation modernity helps us answer the question of why Mitchell’s particular construction of Irish-Southern culture is so resilient—and to move beyond a recognition of the role reversal that occurs when the colonized become the colonizers—by delving further into the novel’s ideological apparatus. Most crucially, a plantation framework that considers Irish and Southern histories illuminates the novel’s construction of transnational white ethnic identity. The plantation allows us to think meaningfully about Gone with the Wind’s relationship to plantation fiction from Ireland and the Caribbean in order to see it as a production of— rather than a retreat from—transatlantic modernity.
The parallel growth of motoneuron axons with the dorsal aorta depends on Vegfc/Vegfr3 signaling in zebrafish
Authors: Kwon Hyouk-Bum , Fukuhara Shigetomo , Asakawa Kazuhide , Ando Koji , Kashiwada Takeru , Kawakami Koichi , Hibi Masahiko , Kwon Young-Guen , Kim Kyu-Won , Alitalo Kari , Mochizuki Naoki
Published: September 2013

Blood vessels and neurons grow often side by side. However, the molecular and cellular mechanisms underlying their parallel development remain unclear. Here, we report that a subpopulation of secondary motoneurons extends axons ventrally outside of the neural tubes and rostrocaudally as a fascicle beneath the dorsal aorta (DA) in zebrafish. We tried to clarify the mechanism by which these motoneuron axons grow beneath the DA and found that Vegfc in the DA and Vegfr3 in the motoneurons were essential for the axon growth. Forced expression of either Vegfc in arteries or Vegfr3 in motoneurons resulted in enhanced axon growth of motoneurons over the DA. Both vegfr3 morphants and vegfc morphants lost the alignment of motoneuron axons with DA. In addition, forced expression of two mutant forms of Vegfr3 in motoneurons, potentially trapping endogenous Vegfc, resulted in failure of growth of motoneuron axons beneath the DA. Finally, a vegfr3 mutant fish lacked the motoneuron axons beneath the DA. Collectively, Vegfc from the preformed DA guides the axon growth of secondary motoneurons.
The mechanical anisotropy in a tissue promotes ordering in hexagonal cell packing
Authors: Sugimura Kaoru , Ishihara Shuji
Published: September 2013

Many epithelial tissues pack cells into a honeycomb pattern to support their structural and functional integrity. Developmental changes in cell packing geometry have been shown to be regulated by both mechanical and biochemical interactions between cells; however, it is largely unknown how molecular and cellular dynamics and tissue mechanics are orchestrated to realize the correct and robust development of hexagonal cell packing. Here, by combining mechanical and genetic perturbations along with live imaging and Bayesian force inference, we investigate how mechanical forces regulate cellular dynamics to attain a hexagonal cell configuration in the Drosophila pupal wing. We show that tissue stress is oriented towards the proximal-distal axis by extrinsic forces acting on the wing. Cells respond to tissue stretching and orient cell contact surfaces with the stretching direction of the tissue, thereby stabilizing the balance between the intrinsic cell junction tension and the extrinsic force at the cell-population level. Consequently, under topological constraints of the two-dimensional epithelial sheet, mismatches in the orientation of hexagonal arrays are suppressed, allowing more rapid relaxation to the hexagonal cell pattern. Thus, our results identify the mechanism through which the mechanical anisotropy in a tissue promotes ordering in cell packing geometry.
Filopodia are dispensable for endothelial tip cell guidance
Authors: Phng Li-Kun , Stanchi Fabio , Gerhardt Holger
Published: September 2013

Actin filaments are instrumental in driving processes such as migration, cytokinesis and endocytosis and provide cells with mechanical support. During angiogenesis, actin-rich filopodia protrusions have been proposed to drive endothelial tip cell functions by translating guidance cues into directional migration and mediating new contacts during anastomosis. To investigate the structural organisation, dynamics and functional importance of F-actin in endothelial cells (ECs) during angiogenesis in vivo, we generated a transgenic zebrafish line expressing Lifeact-EGFP in ECs. Live imaging identifies dynamic and transient F-actin-based structures, such as filopodia, contractile ring and cell cortex, and more persistent F-actin-based structures, such as cell junctions. For functional analysis, we used low concentrations of Latrunculin B that preferentially inhibited F-actin polymerisation in filopodia. In the absence of filopodia, ECs continued to migrate, albeit at reduced velocity. Detailed morphological analysis reveals that ECs generate lamellipodia that are sufficient to drive EC migration when filopodia formation is inhibited. Vessel guidance continues unperturbed during intersegmental vessel development in the absence of filopodia. Additionally, hypersprouting induced by loss of Dll4 and attraction of aberrant vessels towards ectopic sources of Vegfa165 can occur in the absence of endothelial filopodia protrusion. These results reveal that the induction of tip cells and the integration of endothelial guidance cues do not require filopodia. Anastomosis, however, shows regional variations in filopodia requirement, suggesting that ECs might rely on different protrusive structures depending on the nature of the environment or of angiogenic cues.
Improving Underground Mine Access Layouts Using Software Tools
Authors: Brazil Marcus , Grossman Peter , Rubinstein J. Hyam , Thomas Doreen
Published: September 2013

The authors have developed two software tools, PUNO and DOT, for optimally designing the layout of the system of tunnels in an underground mine, known as the access network for the mine. We recently applied these tools, which use principles from geometric optimization, to ore deposits at the Prominent Hill mine in South Australia and the Leeville gold mine in Nevada. When we compared the designs that the tools generated with the designs prepared by mining engineers, we found that our tools generated designs more quickly, were at least as cost efficient, and often revealed new design options by which the engineers’ original designs could be improved.
Salesforce Compensation with Inventory Considerations
Authors: Dai Tinglong , Jerath Kinshuk
Published: September 2013

We study a scenario in which a firm designs the compensation contract for a salesperson who exerts unobservable effort to increase the level of uncertain demand and, jointly, the firm also decides the inventory level to be stocked. We use a newsvendor-type model in which actual sales depend on the realized demand but are limited by the inventory available, and unfulfilled demand cannot be observed. In this setup, under the optimal contract, the agent is paid a bonus for meeting a sales quota. Our key result is that it may be optimal for the firm to stock more than the first-best inventory level, because this enables the firm to obtain a more precise indicator of the salesperson's effort. The possibility of stockouts due to limited inventory also leads to several counterintuitive results, including the following: (i) relative to when stockouts are not considered, it may be optimal for the firm to pay a higher bonus even though limited inventory constrains sales; (ii) as inventory becomes more expensive, thereby forcing the firm to lower its inventory, the firm may nevertheless pay the agent a higher bonus; and (iii) if there is a lower probability that the agent's effort exertion leads to high demand, rather than lowering inventory due to the lower sales potential, the firm may increase inventory.

This paper was accepted by J. Miguel Villas-Boas, marketing.
Novel Spot Tests for Detecting the Presence of Zinc Sulfate in Urine, a Newly Introduced Urinary Adulterant to Invalidate Drugs of Abuse Testing
Authors: Welsh Kerry J. , Dierksen Jennifer E. , Actor Jeffrey K. , Dasgupta Amitava
Published: September 2013

Objectives:

To find a suitable method for detecting zinc sulfate in adulterated urine.

Methods:

Two rapid spot tests to detect the presence of zinc sulfate in urine were developed.

Results:

Addition of 3 to 4 drops of 1N sodium hydroxide solution to approximately 1 mL of urine containing zinc sulfate led to the formation of a white precipitate, which was soluble in excess sodium hydroxide. In the second spot test, addition of 3 to 4 drops of 1% sodium chromate solution to 1 mL of urine containing zinc sulfate followed by the addition of 4 to 5 drops of 1N sodium hydroxide led to formation of a yellow precipitate (zinc chromate). Detection limit of these visual spot tests was 10 mg/mL of zinc sulfate in urine. Twenty drug-free urine specimens and urine containing high amounts of sugar or reducing substances were tested with no false-positive spot test results observed. However, if lead is present in high amounts in urine, it may cause false-positive spot test results. When aliquots of urine controls for drugs of abuse testing were supplemented with different amounts of zinc sulfate, false-negative drug test results were observed except for amphetamine. Zinc sulfate also falsely reduced measured urine alcohol level in urine.

Conclusions:

Zinc sulfate can invalidate urine drug and alcohol testing but can be detected using the novel spot tests developed.
Distinguishing Score 0 From Score 1+ in HER2 Immunohistochemistry-Negative Breast Cancer
Authors: Lambein Kathleen , Van Bockstal Mieke , Vandemaele Lies , Geenen Sofie , Rottiers Isabelle , Nuyts Ann , Matthys Bart , Praet Marleen , Denys Hannelore , Libbrecht Louis
Published: September 2013

Objectives:

To investigate the clinical and pathobiological significance of distinguishing score 0 and score 1+ within the group of immunohistochemistry (IHC)-negative invasive breast cancers.

Methods:

We studied HER2 status using both IHC and fluorescence in situ hybridization (FISH) in 150 consecutive breast tumors submitted to our laboratory after a negative IHC result in local testing centers.

Results:

We were able to discern a group of score 0 tumors that had a lower HER2 copy number than the group consisting of score 1+ tumors. In contrast with the group of score 1+ tumors, HER2 FISH was consistently negative for both copy number–based and ratio-based tumors without equivocal results.

Conclusions:

In a setting with stringent quality assurance, score 0 and score 1+ tumors emerge as distinct and clinically important subgroups within the HER2 IHC-negative population.
Transiently Increased Variation Between a Point-of-Care and Laboratory INR Method After a Long Period of Correlation
Authors: Sephel Gregory C. , Laposata Michael
Published: September 2013

Objectives:

To perform long-term comparison between laboratory Stago and Point-of-Care (POC) i-STAT methods for determining the international normalized ratio (INR).

Methods:

This was a multicenter method comparison of patient INR results and factors related to performance variance.

Results:

For 5 years, the assays demonstrated close patient correlation within and above the 3.5 INR therapeutic range cutoff (bias, 0.23 INR units). Patient results above 3.5 INR were bimodal, with 60% demonstrating an i-STAT INR bias of less than 0.5. Several patient conditions were associated with the presence of a higher i-STAT bias. In year 6, a broader range i-STAT bias developed, increasing to 0.73 INR units. The increased bias persisted for 3 years, then returned to initial levels following i-STAT adjustments. The substantial increase in i-STAT bias after a long period of stability was partly corrected by renewed correlation to the international reference preparation. Additional assay drift is discussed in relation to thromboplastin reagents and other testing variables.

Conclusions:

This study emphasizes the need for continual laboratory correlation with POC devices and caution in using published comparisons.
From Cytomorphology to Molecular Pathology
Authors: Zhang Songlin , Gong Yun
Published: September 2013

Objectives:

The field of cytopathology has been rapidly advancing in the era of molecular pathology and personalized medicine. On-site cytologic evaluation for adequacy and triaging specimens for small core biopsy or fine-needle aspiration (FNA) are often required. Cytopathologists face the challenge of how to best triage small specimens for diagnosis, molecular testing, and personalized treatment. Owing to its minimally invasive nature, FNA alone or combined with core biopsy for lymphoproliferative disorders and soft tissue tumors has gained popularity.

Methods:

Literature review and author’s institutional experience are used for this review article. This article will focus mainly on lymphoproliferative disorders and soft tissue tumors.

Results:

Evaluation combining cytomorphology, immunohistochemistry, and/or molecular pathology is often needed to accurately diagnose and classify lymphomas and soft tissue tumors. Many molecular tests have been performed on cytologic specimens, such as tests for BRAF and RET in thyroid FNA.

Conclusions:

Molecular pathology has been widely integrated into conventional cytopathology for diagnosing lymphoproliferative disorders and soft tissue tumors, and the diagnostic value of FNA on those tumors has increased significantly. Cytology will play a more important role in the era of personalized medicine,
Neutrophil CD64 for Daily Surveillance of Systemic Infection and Necrotizing Enterocolitis in Preterm Infants
Authors: Lam Hugh Simon , Cheung Hon Ming , Poon Terence Chuen Wai , Wong Raymond Pui On , Leung Kam Tong , Li Karen , Ng Pak Cheung
Published: September 2013

BACKGROUND

Early detection and treatment of infected preterm infants could decrease morbidity and mortality. Neutrophil CD64 has been shown to be an excellent early diagnostic biomarker of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC). We aimed to study whether using CD64 as a daily surveillance biomarker could predict LOS/NEC before clinical manifestation.

METHODS

We collected 0.1 mL whole blood from very low birth weight (VLBW) infants from day 7 postnatal age until routine daily blood tests were no longer required. Four categories of responses were defined: proven sepsis, clinical sepsis, nonsepsis/non-NEC, and asymptomatic CD64 activation.

RESULTS

A total of 146 infants were consecutively recruited and 155 episodes of sepsis evaluation were performed. The biomarker screening utility, sensitivity, specificity, positive predictive value, and negative predictive value for surveillance of LOS/NEC using a cutoff of 5655 antibody-PE (phycoerythrin) molecules bound/cell were 89%, 98%, 41%, and 99.8%, respectively. LOS/NEC was detected a mean of 1.5 days before clinical presentation. However, 63 episodes of CD64 activation occurred in asymptomatic infants who would not otherwise have required sepsis evaluations.

CONCLUSIONS

As a surveillance biomarker, neutrophil CD64 detected LOS/NEC 1.5 days before clinical presentation, but at the expense of performing 41% additional sepsis evaluations. This was mainly attributed to an unexpected group of asymptomatic infants with CD64 activation, who recovered spontaneously and did not require antimicrobial treatment. The latter group has not been previously recognized in VLBW infants and could represent subclinical infection secondary to transient bacterial translocation or mild viral infection.
Community Language Classes: How Ready are Students for More Technology?
Authors: Ratz Sibylle
Published: September 2013

Are students at community language classes ready to use more technology for their learning? Although research into the use of technology in many language learning settings is widespread, the particular needs of the diverse body of community classes which are open to all have received little attention. This article reports on a survey on technological preconditions (e-readiness) prior to introducing more technology to community language classes at a large UK university.Results showed that almost all students were extremely e-ready in regard to physical access to computers and competence with basic word processing applications. However, only 50% used more sophisticated applications, such as chat, discussions or gaming. 66% regularly updated their computer skills and were very motivated and confident computer users. There was a strong interest (over 90%) in the introduction of more computer-based resources for language learning. The introduction of blended learning was of interest to 75% of learners.Older participants, and those not in the labour force, displayed a lower degree of e-readiness, particularly regarding their skills and confidence. They were also slightly less interested in the introduction of online resources. Women displayed less confidence than men.Implications for the introduction and choice of technologies for community language learners are discussed.
Risks to Informed Consent in Pedagogic Research
Authors: Regan Julie-Anne
Published: September 2013

Stierer & Antoniou (2004) have described Pedagogic Research (PR) as primarily teachers undertaking research into aspects of their own teaching and learning. Consequently, those undertaking PR often occupy dual roles of teacher and researcher. Likewise the subjects being studied are often the researcher’s own students and thus also occupying dual roles of student and participant. The purpose of this article is to highlight the potential risks to valid, informed consent inherent in the nature of pedagogic research itself; due to the dual roles mentioned above and the blurred boundaries between practice development and PR. Whilst inaccurate or incomplete information for decision making is an obvious risk to informed consent, the risks to voluntary participation can be more subtle. Reference is made to a documentary analysis of feedback provided to applicants by a research ethics committee reviewing pedagogic research. Whilst this is not a research report of that study, it provides empirical evidence to support the arguments made in this article. The article concludes that the greatest risk to valid informed consent is the lack of awareness among practitioner-researchers of the risks to voluntary participation this type of research holds. The author highlights the role for academic developers in highlighting these issues on professional development programmes. It is also recommended that a clear institutional position on when teacher/researchers need to apply for ethical approval could also be useful, particularly if flexibility is built in to allow for informal discussions with the Chair of the REC.
Editorial
Authors: Stefani Lorraine
Published: September 2013

June 2013 Editorial for Journal of Perspectives in Applied Academic Practice
Clueless in Academe: How Schooling Obscures the Life of the Mind
Authors: Tierney Anne Margaret
Published: September 2013

Book review of Clueless in Academe: How Schooling Obscures the Life of the Mind, Gerald Graff, Yale University Press, New Haven and London, 2003
Editors' Welcome
Authors: Editors JPAAP
Published: September 2013

Welcome to the launch issue of the Journal of Perspectives in Applied Academic Practice.
Effect of Titanium on Homogenizing Process and Microstructure of Alloy 2618
Authors: Liu Tingting , Liu Ya , Su Xuping , Peng Haoping , Wang Jianhua
Published: September 2013

The effect of titanium on the homogenizing process of alloy 2618 and the microstructure of the Ti-containing alloy before and after homogenization has been investigated using optical microscope (OM), scanning electron microscope (SEM), energy dispersive X-ray (EDX), differential thermal analysis (DTA). The results show that the addition of 1.5 mass% Ti to alloy 2618 could refine its grain size remarkably. A large amount of rod-shape Al3Ti particles with the size range of 2–12 μm distribute evenly and dispersively in the alloy. It is θ (Al2Cu) phase instead of S' (Al2CuMg) obtained in eutectic structures due to the non-equilibrium solidification in casting of 2618-Ti alloy, which is the same as alloy 2618. The optimal homogenization temperature (773 K) for Ti-containing alloy 2618 (2618-Ti alloy) is the same as that of alloy 2618. Combining the results of kinetic analysis and experiments, the optimized homogenizing time for Ti-containing alloy 2618 at 773 K is only 12 h, which is shorter than that for alloy 2618. The shortening of the optimized homogenizing time results mainly from the decrease of the grain size of 2618-Ti alloy.
An Exact, Fully Nonlinear Solution of the Poisson-Boltzmann Equation with Anti-symmetric Electric Potential Profiles
Authors: Chow Kwok Wing , Chu Henry C. W. , Ng Chiu-On
Published: September 2013

The electric potential in an electro-osmotic flow is governed by the Poisson-Boltzmann (P-B) equation. A new solution is obtained by solving the fully nonlinear P-B model in a rectangular channel using the Hirota bilinear method, without invoking the Debye-Hückel (D-H) (linearization) approximation. This new solution is anti-symmetric about the centerline of two parallel plates, representing the case of opposite charges on two walls of a microchannel. The electric potentials and velocity fields derived from both the complete and linearized P-B equations are compared. Significant deviations are revealed, in particular for cases with high zeta potential. If a boundary slip on the wall is permitted, the electro-osmotic flow corresponding to this anti-symmetric wall potential can still induce a net fluid flow. These results will have important applications in characterizing bi-directional flows within microchannels, capillary tubes, membranes and porous materials.
Contextual effect of repression of bone morphogenetic protein activity in prostate cancer
Authors: Pham Linda Kim , Liang Mengmeng , Adisetiyo Helty A , Liao Chun-Peng , Cohen Michael B , Tahara Stanley M , Frenkel Baruch , Kasahara Noriyuki , Roy-Burman Pradip
Published: September 2013

Several studies have focused on the effect of bone morphogenetic protein (BMP) on prostate cancer homing and growth at distant metastatic sites, but very little effect at the primary site. Here, we used two cell lines, one (E8) isolated from a primary tumor and the other (cE1) from a recurrent tumor arising at the primary site, both from the conditionalPtendeletion mouse model of prostatic adenocarcinoma. Over-expression of the BMP antagonist noggin inhibited proliferation of cE1 cellsin vitrowhile enhancing their ability to migrate. On the other hand, cE1/noggin grafts grownin vivoshowed a greater mass and a higher proliferation index than the cE1/control grafts. For suppression of BMP activity in the context of cancer-associated fibroblasts (CAFs), we used noggin-transduced CAFs from the same mouse model to determine their effect on E8- or cE1-induced tumor growth. CAF/noggin led to increased tumor mass and greater de-differentiation of the E8 cell when compared with tumors formed in the presence of CAF/control cells. A trend of increase in the size of the tumor was also noted for cE1 cells when inoculated with CAF/noggin. Together, the results may point to a potential inhibitory role of BMP in the growth or re-growth of prostate tumor at the primary site. Additionally, results for cE1/noggin, and cE1 mixed with CAF/noggin, suggested that suppression of BMP activity in the cancer cells may have a stronger growth-enhancing effect on the tumor than its suppression in the fibroblastic compartment of the tumor microenvironment.
Oral Dexamethasone for Bronchiolitis: A Randomized Trial
Authors: Alansari Khalid , Sakran Mahmoud , Davidson Bruce L. , Ibrahim Khalid , Alrefai Mahmoud , Zakaria Ibrahim
Published: September 2013

OBJECTIVE:

Determine whether dexamethasone treatment added to salbutamol reduces time to readiness for discharge in patients with bronchiolitis and possible asthma.

METHODS:

We compared efficacy and safety of dexamethasone, 1 mg/kg, then 0.6 mg/kg for 4 more days, with placebo for acute bronchiolitis in patients with asthma risk, as determined by eczema or a family history of asthma in a first-degree relative. All patients received inhaled salbutamol. Time to readiness for discharge was the primary efficacy outcome.

RESULTS:

Two hundred previously healthy infants diagnosed with bronchiolitis, median age 3.5 months, were enrolled. Five placebo recipients needed admission to intensive care unit during infirmary treatment (P = .02). Among 100 dexamethasone recipients, geometric mean time to readiness for discharge was 18.6 hours (95% confidence interval [CI], 14.9 to 23.1 hours); among 90 control patients, 27.1 hours (95% CI, 21.8 to 33.8 hours). The ratio, 0.69 (95% CI, 0.51 to 0.93), revealed a mean 31% shortening of duration to readiness for discharge favoring dexamethasone (P = .015). Twenty-two dexamethasone and 19 control patients were readmitted to the short stay infirmary in the week after discharge (P = .9). No hospitalizations or side effects were reported during 7 days of surveillance.

CONCLUSIONS:

Dexamethasone with salbutamol shortened time to readiness for infirmary discharge during bronchiolitis episodes in patients with eczema or a family history of asthma in a first-degree relative. Infirmary and clinic visits in the subsequent week occurred similarly for the 2 groups.
Time Dependent Parallel Resistance in an Organic Schottky Contact
Authors: Takshi Arash , Madden John D. , Fok Chi Wah Eddie , Warren Mya
Published: September 2013

The DC characteristics of a Schottky contact between regioregular poly (3-hexylthiophene) and aluminum are studied in forward and reverse bias regimes. Current-voltage curves of the junction in reverse bias show a resistive path in parallel with the expected Schottky contact. This is the sign of a nonuniform junction between the metal and semiconductor that exhibits ohmic behavior in some regions. Reduction of this parallel resistance and degradation of the Schottky junction are observed over a period of two weeks. Accumulation of undesired ions in the polymer or diffusion of aluminum atoms into the semiconductor are two possible mechanisms which may explain the time dependent behavior of these Schottky junctions.