bluuebunny/crossref_metadata_2025 huggingface dataset:
An ethnobotanical study of medicinal plants used in Kilte Awulaelo District, Tigray Region of Ethiopia
Authors: Teklay Abraha , Abera Balcha , Giday Mirutse
Published: September 2013

Background

The Ethiopian people have been dependent on traditional medicine, mainly medicinal plants, from time immemorial for control of human and animal health problems, and they still remain to be largely dependent on the practice. The purpose of the current study was to conduct ethnobotanical study to document medicinal plants used to treat diseases of human and domestic animals in Kilte Awulaelo District in the Tigray Region of Ethiopia.

Methods

Ethnobotanical data were collected between July and September 2011 through semi-structured interviews, ranking exercises and field observations. For the interviews, 72 knowledgeable informants were sampled using purposive sampling method. For the different ranking exercises, key informants were identified with the help of elders and local administrators from informants that were already involved in the interviews.

Results

The study revealed 114 medicinal plant species belonging to 100 genera and 53 families. The plants were used to treat 47 human and 19 livestock diseases. Of the species, the majority (74%) were obtained from the wild. Herbs were the most utilized plants, accounting for 44% of the species, followed by shrubs (29%). Leaf was the most commonly used plant part accounting for 42.98% of the plants, followed by roots (25.73%). Preference ranking exercise on selected plants used against abdominal pain indicated the highest preference of people for Solanum marginatum. Direct matrix ranking showed Cordia africana as the most preferred multipurpose plant in the community. Preference ranking of selected scarce medicinal plants indicated Myrica salicifolia as the most scarce species, followed by Boscia salicifolia and Acokanthera schimperi. According to priority ranking, drought was identified as the most destructive factor of medicinal plants, followed by overgrazing and firewood collection.

Conclusion

Medicinal plants are still playing significant role in the management of various human and livestock diseases in the study area with herbs taking the lead in the number of plants used in the preparation of remedies, which may be an indication of their relatively better abundance as compared to other life forms. Recurrent drought was reported to have seriously threatened medicinal plant resources in the District. Awareness is thus needed be raised among local people on sustainable utilization and management of plant resources. Ex situ and in situ conservation measures should be taken to protect the medicinal plants of the District from further destruction and special attention should be given to the medicinal plants that were indicated by preference ranking exercise as the most threatened ones.
Wild boar tuberculosis in Iberian Atlantic Spain: a different picture from Mediterranean habitats
Authors: Muñoz-Mendoza Marta , Marreros Nelson , Boadella Mariana , Gortázar Christian , Menéndez Santiago , de Juan Lucía , Bezos Javier , Romero Beatriz , Copano María Francisca , Amado Javier , Sáez José Luis , Mourelo Jorge , Balseiro Ana
Published: September 2013

Background

Infections with Mycobacterium bovis and closely related members of the Mycobacterium tuberculosis complex (MTC) are shared between livestock, wildlife and sporadically human beings. Wildlife reservoirs exist worldwide and can interfere with bovine tuberculosis (TB) eradication efforts. The Eurasian wild boar (Sus scrofa) is a MTC maintenance host in Mediterranean Iberia (Spain and Portugal). However, few systematic studies in wild boar have been carried out in Atlantic regions. We describe the prevalence, distribution, pathology and epidemiology of MTC and other mycobacteria from wild boar in Atlantic Spain. A total of 2,067 wild boar were sampled between 2008 and 2012.

Results

The results provide insight into the current status of wild boar as MTC and Mycobacterium avium complex (MAC) hosts in temperate regions of continental Europe. The main findings were a low TB prevalence (2.6%), a low proportion of MTC infected wild boar displaying generalized TB lesions (16.7%), and a higher proportion of MAC infections (4.5%). Molecular typing revealed epidemiological links between wild boar and domestic – cattle, sheep and goat – and other wildlife – Eurasian badger (Meles meles) and red fox (Vulpes vulpes) – hosts.

Conclusions

This study shows that the likelihood of MTC excretion by wild boar in Atlantic habitats is much lower than in Mediterranean areas. However, wild boar provide a good indicator of MTC circulation and, given the current re-emergence of animal TB, similar large-scale surveys would be advisable in other Atlantic regions of continental Europe.
Endoscopic obstruction is associated with higher risk of acute events requiring emergency operation in colorectal cancer patients
Authors: Chalieopanyarwong Virote , Boonpipattanapong Teeranut , Prechawittayakul Paradee , Sangkhathat Surasak
Published: September 2013

Introduction

Unplanned emergency operations in colorectal cancers (CRC) are generally associated with increased risk of operative complications. This study aimed to examine the association, if any, between an endoscopic finding of obstructing tumor and the subsequent need for an emergency operation, with the aim of determining if this finding could be useful in identifying CRC cases who are more likely to require an emergency operation.

Methods

The records of CRC cases operated on in our institute during the years 2002-2011 were retrospectively reviewed regarding an endoscopic obstruction (eOB), defined as a luminal obstruction of the colon or rectum severe enough to prevent the colonoscope from passing beyond the tumor. The eOBs were analyzed against outcomes in terms of need for emergency operation, surgical complications and overall survival (OS).

Results

A total of 329 CRCs which had been operated on during the study period had complete colonoscopic data. eOB was diagnosed in 209 cases (64%). Occurrence of eOB was not correlated with clinical symptoms. Colon cancer had a higher incidence of eOB (70%) than rectal cases (50%) (p-value < 0.01). eOB was significantly associated with higher tumor size and more advanced T-stage (p < 0.01). Twenty-two cases (7%) had required an emergency operation before their scheduled elective surgery. The cases with eOB had a significantly higher risk of requiring an emergency operation while waiting for their scheduled procedure (p-value < 0.01), and these emergency surgeries had more post-operative complications (36%) than elective procedures (13%) (p-value 0.01) and poorer OS (p-value < 0.01).

Conclusion

Regardless of the presenting symptom, luminal obstruction severe enough to prevent further passage of a colonoscope should prompt the physician to consider an urgent surgery.
Anti-Candida properties of asaronaldehyde of Acorus gramineus rhizome and three structural isomers
Authors: Rajput Sandeep B , Shinde Ravikumar B , Routh Madhushree M , Karuppayil Sankunny M
Published: September 2013

Background

Asaronaldehyde (2, 4, 5-trimethoxybeznaldehyde) is an active component of Acorus gramineus rhizome. This study aims to evaluate the anti-Candida efficacy of asaronaldehyde and its three structural isomers, namely, 2, 3, 4-trimethoxybenzaldehyde, 3, 4, 5-trimethoxybenzaldehyde, and 2, 4, 6- trimethoxybenzaldehyde.

Methods

Susceptibility testing of test compounds was carried out using standard methodology (M27-A2) as per clinical and laboratory standards institute guidelines. Minimum fungicidal concentration (MFC) was determined as the lowest concentration of drug killing 99.9% of Candida cells. The effect on sterol profile was evaluated using the ergosterol quantitation method. Effects on morphogenesis, adhesion and biofilm formation in C. albicans were studied using germ-tube, adherence and biofilm formation assays respectively. Cytotoxicity of test compounds to human RBCs was determined by hemolysis assay.

Results

2, 4, 6-Trimethoxybenzaldehyde exhibited significant anti-Candida activity (P = 0.0412). Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were established as 0.25 and 0.5 mg/mL, respectively. All of the test compounds showed significant inhibition of hyphal form transition in yeast at MIC/2 and MIC/4 values. 3, 4, 5-Trimethoxybenzaldehyde and 2, 4, 6-trimethoxybenzaldehyde inhibited adhesion and biofilms. A hemolytic assay of these compounds revealed that they were non-toxic at MIC values. Asaronaldehyde reduced sterol content.

Conclusion

Asaronaldehyde and 2, 4, 6-trimethoxybenzaldehyde showed anti-Candida efficacy.
Associated factors and comorbidities in patients with pyoderma gangrenosum in Germany: a retrospective multicentric analysis in 259 patients
Authors: Al Ghazal Philipp , Herberger Katharina , Schaller Jörg , Strölin Anke , Hoff Norman-Philipp , Goerge Tobias , Roth Hannelore , Rabe Eberhard , Karrer Sigrid , Renner Regina , Maschke Jan , Horn Thomas , Hepp Julia , Eming Sabine , Wollina Uwe , Zutt Markus , Sick Isabell , Splieth Benno , Dill Dorothea , Klode Joachim , Dissemond Joachim
Published: September 2013

Background

Pyoderma gangrenosum (PG) is a rarely diagnosed ulcerative neutrophilic dermatosis with unknown origin that has been poorly characterized in clinical studies so far. Consequently there have been significant discussions about its associated factors and comorbidities. The aim of our multicenter study was to analyze current data from patients in dermatologic wound care centers in Germany in order to describe associated factors and comorbidities in patients with PG.

Methods

Retrospective clinical investigation of patients with PG from dermatologic wound care centers in Germany.

Results

We received data from 259 patients with PG from 20 different dermatologic wound care centers in Germany. Of these 142 (54.8%) patients were female, 117 (45.2%) were male; with an age range of 21 to 95 years, and a mean of 58 years. In our patient population we found 45.6% with anemia, 44.8% with endocrine diseases, 12.4% with internal malignancies, 9.3% with chronic inflammatory bowel diseases and 4.3% with elevated creatinine levels. Moreover 25.5% of all patients had a diabetes mellitus with some aspects of potential association with the metabolic syndrome.

Conclusions

Our study describes one of the world’s largest populations with PG. Beside the well-known association with chronic bowel diseases and neoplasms, a potentially relevant new aspect is an association with endocrine diseases, in particular the metabolic syndrome, thyroid dysfunctions and renal disorders. Our findings represent clinically relevant new aspects. This may help to describe the patients’ characteristics and help to understand the underlying pathophysiology in these often misdiagnosed patients.
Erdheim-Chester Disease: a comprehensive review of the literature
Authors: Mazor Roei D , Manevich-Mazor Mirra , Shoenfeld Yehuda
Published: September 2013

Erdheim-Chester Disease (ECD) is a rare form of non Langerhans' cell histiocytosis. Individuals affected by this disease are typically adults between their 5th and 7th decades of life. Males and females are almost equally affected. The multi systemic form of ECD is associated with significant morbidity, which may arise due to histiocytic infiltration of critical organ systems. Among the more common sites of involvement are the skeleton, central nervous system, cardiovascular system, lungs, kidneys (retroperitoneum) and skin. The most common presenting symptom of ECD is bone pain. The etiology of ECD is unknown yet thought to be associated with an intense TH1 immune response. It may also be associated with the V600E BRAF mutation, as described in as many as half of the patients in recent studies. Bilateral symmetric increased tracer uptake on 99mTc bone scintigraphy affecting the periarticular regions of the long bones is highly suggestive of ECD. However, definite diagnosis of ECD is established only once CD68(+), CD1a(−) histiocytes are identified within a biopsy specimen. At present, this obscure ailment embodies numerous challenges to medical science. Given its rarity, it is diagnostically elusive and requires a high level of clinical suspicion. Therapeutically, it is of limited alternatives. Currently, interferon-α is the most extensively studied agent in the treatment of ECD and serves as the first line of treatment. Treatment with other agents is based on anecdotal case reports and on the basis of biological rationale. Nevertheless, cladribine (2CDA), anakinra and vemurafenib are currently advocated as promising second line treatments for patients whose response to interferon-α is unsatisfactory. Overall, the 5 year survival of ECD is 68%. Herein, the authors mustered and brought about a panoramic consolidation of all the relevant facts regarding ECD. This work highlights the different clinical, radiological and pathological manifestations associated with ECD, the differential diagnoses, the various treatment options and the acknowledged science explaining the disease.
Methodological challenges in monitoring new treatments for rare diseases: lessons from the cryopyrin-associated periodic syndrome registry
Authors: Tilson Hugh , Primatesta Paola , Kim Dennis , Rauer Barbara , Hawkins Philip N , Hoffman Hal M , Kuemmerle-Deschner Jasmin , van der Poll Tom , Walker Ulrich A
Published: September 2013

Background

The Cryopyrin-Associated Periodic Syndromes (CAPS) are a group of rare hereditary autoinflammatory diseases and encompass Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), and Neonatal Onset Multisystem Inflammatory Disease (NOMID). Canakinumab is a monoclonal antibody directed against IL-1 beta and approved for CAPS patients but requires post-approval monitoring due to low and short exposures during the licensing process. Creative approaches to observational methodology are needed, harnessing novel registry strategies to ensure Health Care Provider reporting and patient monitoring.

Methods

A web-based registry was set up to collect information on long-term safety and effectiveness of canakinumab for CAPS.

Results

Starting in November 2009, this registry enrolled 241 patients in 43 centers and 13 countries by December 31, 2012. One-third of the enrolled population was aged < 18; the overall population is evenly divided by gender. Enrolment is ongoing for children.

Conclusions

Innovative therapies in orphan diseases require post-approval structures to enable in depth understanding of safety and natural history of disease. The rarity and distribution of such diseases and unpredictability of treatment require innovative methods for enrolment and follow-up. Broad international practice-based recruitment and web-based data collection are practical.
Metformin decreases the incidence of ovarian hyperstimulation syndrome: an experimental study
Authors: Elia Evelin M , Quintana Ramiro , Carrere Carlos , Bazzano María V , Rey-Valzacchi Gastón , Paz Dante A , Pustovrh María C
Published: September 2013

Background

In assisted reproduction cycles, gonadotropins are administered to obtain a greater number of oocytes. A majority of patients do not have an adverse response; however, approximately 3-6% develop ovarian hyperstimulation syndrome (OHSS). Metformin reduces the risk of OHSS but little is known about the possible effects and mechanisms of action involved.

Objective

To evaluate whether metformin attenuates some of the ovarian adverse effects caused by OHSS and to study the mechanisms involved.

Material and methods

A rat OHSS model was used to investigate the effects of metformin administration. Ovarian histology and follicle counting were performed in ovarian sections stained with Masson trichrome. Vascular permeability was measured by the release of intravenously injected Evans Blue dye (EB). VEGF levels were measured by commercially immunosorbent assay kit. COX-2 protein expression was evaluated by western blot and NOS levels were analyses by immunohistochemistry.

Results

Animals of the OHSS group showed similar physiopathology characteristics to the human syndrome: increased body weight, elevated progesterone and estradiol levels (P<0.001), increased number of corpora lutea (P<0.001), higher ovarian VEGF levels and vascular permeability (P<0.001 and P<0.01); and treatment with metformin prevented this effect (OHSS+M group; P<0.05). The vasoactive factors: COX-2 and NOS were increased in the ovaries of the OHSS group (P<0.05 and P<0.01) and metformin normalized their expression (P<0.05); suggesting that metformin has a role preventing the increased in vascular permeability caused by the syndrome.

Conclusion

Metformin has a beneficial effect preventing OHSS by reducing the increase in: body weight, circulating progesterone and estradiol and vascular permeability. These effects of metformin are mediated by inhibiting the increased of the vasoactive molecules: VEGF, COX-2 and partially NOS. Molecules that are increased in OHSS and are responsible for a variety of the symptoms related to OHSS.
Evaluation of serum Amphiregulin levels in breast cancer patients and cancer-free controls
Authors: Peterson Esther A , Pectasides Eirini , Shabbeer Shabana , Wiechmann Lisa , Sparano Joseph A , Kenny Paraic A
Published: September 2013

Background

Expression of the Epidermal Growth Factor Receptor ligand, Amphiregulin, has been associated with estrogen receptor positive breast cancer. As Amphiregulin is proteolytically released from the surface of breast cancer cells, we investigated the levels of Amphiregulin in the serum of breast cancer patients and cancer-free women to evaluate its potential utility as a breast cancer biomarker.

Findings

Serum Amphiregulin levels were quantified by ELISA from 125 cancer-free women and 114 breast cancer patients. No significant association between serum Amphiregulin levels and breast cancer status was detected at two cut-points evaluated.

Conclusions

Measurement of serum Amphiregulin levels lacks the necessary sensitivity and specificity for breast cancer screening in the general population.
Accessory renal arteries in a Caribbean population: a computed tomography based study
Authors: Johnson Peter B , Cawich Shamir O , Shah Sundeep D , Aiken William , McGregor Roy G , Brown Hilary , Gardner Michael T
Published: September 2013

Introduction

The commonest variation to the classic anatomic description of renal arterial supply is the presence of accessory renal arteries. The incidence varies widely according to ethnicity. There is no data on the prevalence of these anomalies in persons of Caribbean ethnicity.

Methods

All CT scans done over two years from July 1, 2010 to June 30, 2012 were retrospectively evaluated. The anatomy of the renal arterial supply was reported from these studies and the anatomy of accessory renal arteries was documented.

Results

There were 302 CT scans evaluated and accessory renal arteries were present in 109/302 (36.1%) CT scans, 95% confidence interval 30.6%, 41.4%. There were 71/309 (23.5%) patients with accessory arteries on the left and 54/309 (17.9%) had them on the right (p 0.087). Of these, 16 (14.7%) patients had bilateral accessory renal arteries present. The most common origin for the accessory arteries was the abdominal aorta in 108 (99.1%) cases and in 1 case the accessory artery arose from the coeliac trunk. There were 80 left sided accessory renal arteries: 17 (21.3%) upper polar and 27 (33.8%) lower polar arteries. Of 62 right sided accessory arteries, 14 (22.6%) were upper polar and 26 (42%) were lower polar arteries.

Conclusion

This is the first population-based report of anatomic anomalies in renal arterial supply in a Caribbean population. These are important findings that may affect vascular and urologic procedures on persons of Caribbean ethnicity.
The potential impact of adding genetic markers to clinical parameters in managing high-risk prostate cancer patients
Authors: Alvarez-Cubero Maria Jesus , Martinez-Gonzalez Luis Javier , Vazquez-Alonso Fernando , Saiz Maria , Alvarez Juan Carlos , Lorente Jose Antonio , Cozar Jose Manuel
Published: September 2013

Purpose

High-risk prostate cancer is a potentially lethal disease that is increasing in the diagnosis of prostate cancer patients. Compared to other prostate cancer patients (medium or low risk), management, diagnosis and treatment are not as successful among high-risk patients. Because the genetic characterization of prostate cancer patients is increasing, we aimed to determine whether genetic information in one of the primary associated genes, such as RNASEL (2', 5'-oligoadenylate-dependent RNase L), could be used as a biomarker to improve the quality of life and treatment among high-risk patients. The main objective is to identify genetic variants of RNASEL that could be associated with high-risk prostate cancer to improve the clinical managing of these patients.

Methods

A total of 231 prostate cancer patients were genotyped for 7 variants of RNASEL gene. Clinical information was obtained from medical examinations and genetic analysis (amplification and sequencing 7 variants of RNASEL gene) were performed by the researchers. Data were processed by statistical analysis (Chi square and logistic regression) using SPSS v.15.0.

Results

Comparisons between genotypes and clinical characteristics of patients revealed that individuals with GG in D541E, AA in R462Q and AG in I97L in RNASEL gene were high-risk patients according to the European Urology Guidelines.

Conclusions

Genotyping the RNASEL gene with routine diagnostic techniques could confer a more precise diagnosis of high-risk prostate cancer patients and increase the diagnostic accuracy above the current rate of 70% due to the relation between the genetic variants of RNASEL gene and the risk of this cancer.
Opposite regulatory effects of IFN-β and IL-3 on C-type lectin receptors, antigen uptake, and phagocytosis in human macrophages
Authors: Cardone Marco , Ikeda Kyojiro N , Varano Barbara , Belardelli Filippo , Millefiorini Enrico , Gessani Sandra , Conti Lucia
Published: September 2013

CLRs are predominantly expressed in macrophages and myeloid DCs, where they play a key role in antigen recognition, scavenging, and host defense against pathogens. To identify novel immunoregulatory cytokines and networks involved in the control of these functions, we analyzed the coordinate effects of IFN-β and IL-3 on CLR expression, antigen uptake, and phagocytosis in human MDMs and MDDCs. We report that these cytokines exert opposite regulatory effects on the expression of CLRs and endocytic/phagocytic activities of MDMs. Specifically, IFN-β markedly inhibits the expression of MR and Dectin-1 during MDM differentiation and impairs the capacity of MDM to internalize antigens and phagocytose unopsonized Candida albicans. Conversely, IL-3 up-modulates MR, Dectin-1, and DC-SIGN, thus allowing more efficient uptake/phagocytosis. Interestingly, IL-3 counteracts the IFN-β effect on antigen uptake/processing by fully restoring MR expression in IFN-β-primed MDMs. In contrast, the phagocytic activity is only partially restored as a result of the failure of IL-3 in counteracting IFN-β-induced Dectin-1 suppression. Notably, IFN-β-mediated impairment of CLR expression/function occurs in macrophages but not in MDDCs. These results identify IFN-β and IL-3 as unrecognized regulators of CLR expression and function, unraveling a novel interaction between these cytokines instrumental for the regulation of the macrophage response to pathogens.
Temporal windowing and inverse transform of the wavefield in the Laplace-Fourier domain
Authors: Kwak Sangmin , Jun Hyunggu , Ha Wansoo , Shin Changsoo
Published: September 2013

Temporal windowing is a valuable process, which can help us to focus on a specific event in a seismogram. However, applying the time window is difficult outside the time domain. We suggest a windowing method which is applicable in the Laplace-Fourier domain. The window function we adopt is defined as a product of a gain function and an exponential damping function. The Fourier transform of a seismogram windowed by this function is equivalent to the partial derivative of the Laplace-Fourier domain wavefield with respect to the complex damping constant. Therefore, we can obtain a windowed seismogram using the partial derivatives of the Laplace-Fourier domain wavefield. We exploit the time-windowed wavefield, which is modeled directly in the Laplace-Fourier domain, to reconstruct subsurface velocity model by waveform inversion in the Laplace-Fourier domain. We present the windowed seismograms by introducing an inverse Laplace-Fourier transform technique and demonstrate the effect of temporal windowing in a synthetic Laplace-Fourier domain waveform inversion example.
Integrated geophysical investigation of the St. James Fault Complex: A case study
Authors: Jacob Robert W. , Byler Jeremy B. , Gray Mary Beth
Published: September 2013

We noninvasively detected the characteristics and location of a regional fault in an area of poor bedrock exposure complicated by karst weathering features in the subsurface. Because this regional fault is associated with sinkhole formation, its location is important for hazard avoidance. The bedrock lithologies on either side of the fault trace are similar; hence, we chose an approach that capitalized on the complementary strengths of very low frequency (VLF) electromagnetic, resistivity, and gravity methods. VLF proved most useful as a first-order reconnaissance tool, allowing us to define a narrow target area for further geophysical exploration. Fault-related epikarst was delineated using resistivity. Ultimately, a high-resolution gravity survey and subsequent inverse modeling using the results of the resistivity survey helped to further constrain the location and approximate orientation of the fault. The combined results indicated that the location of the fault trace needed to be adjusted 53 m south of the current published location and was consistent with a north-dipping thrust fault. Additionally, a gravity low south of the fault trace agreed with the location of conductive material from the resistivity and VLF surveys. We interpreted these anomalies to represent enhanced epikarst in the fault footwall. We clearly found that a staged approach involving a progression of methods beginning with a reconnaissance VLF survey, followed by high-resolution gravity and electrical resistivity surveys, can be used to characterize a fault and fault-related karst in an area of poor bedrock surface exposure.
Surface-consistent matching filters for time-lapse seismic processing
Authors: Almutlaq Mahdi H. , Margrave Gary F.
Published: September 2013

We evaluated the concept of surface-consistent matching filters for processing time-lapse seismic data, in which matching filters are convolutional filters that minimize the sum-squared error between two signals. Because in the Fourier domain a matching filter is the spectral ratio of the two signals, we extended the well-known surface-consistent hypothesis such that the data term is a trace-by-trace spectral ratio of two data sets instead of only one (i.e., surface-consistent deconvolution). To avoid unstable division of spectra, we computed the spectral ratios in the time domain by first designing trace-sequential, least-squares matching filters, then Fourier transforming them. A subsequent least-squares solution then factored the trace-sequential matching filters into four operators: two surface-consistent (source and receiver) and two subsurface-consistent (offset and midpoint). We evaluated a time-lapse synthetic data set with nonrepeatable acquisition parameters, complex near-surface geology, and a variable subsurface reservoir layer. We computed the four-operator surface-consistent matching filters from two surveys, baseline and monitor, then applied these matching filters to the monitor survey to match it to the baseline survey over a temporal window where changes were not expected. This algorithm significantly reduced the effect of most of the nonrepeatable parameters, such as differences in source strength, receiver coupling, wavelet bandwidth and phase, and static shifts. We computed the normalized root mean square difference on raw stacked data (baseline and monitor) and obtained a mean value of 70%. This value was significantly reduced after applying the 4C surface-consistent matching filters to about 13.6% computed from final stacks.
Laboratory measurements of low- and high-frequency elastic moduli in Fontainebleau sandstone
Authors: David Emmanuel C. , Fortin Jérome , Schubnel Alexandre , Guéguen Yves , Zimmerman Robert W.
Published: September 2013

The presence of pores and cracks in rocks causes the fluid-saturated wave velocities in rocks to be dependent on frequency. New measurements of the bulk modulus at low frequencies (0.02–0.1 Hz) were obtained in the laboratory using oscillation tests carried out on two hydrostatically stressed Fontainebleau sandstone samples, in conjunction with ultrasonic velocities and static measurements, under a range of differential pressures (10–95 MPa), and with three different pore fluids (argon, glycerin, and water). For the 13% and 4% porosity samples, under glycerin- and water-saturated conditions, the low-frequency bulk modulus at 0.02 Hz matched well the low-frequency and ultrasonic dry bulk modulus. The glycerin- and water-saturated samples were much more compliant at low frequencies than at high frequencies. The measured bulk moduli of the tested rocks at low frequencies (0.02–0.1 Hz) were much lower than the values predicted by the Gassmann equation. The frequency dispersion of the P and S velocities was much higher at low differential pressures than at high pressures, due to the presence of open cracks at low differential pressures.
Phase Ib Study of Panobinostat and Bortezomib in Relapsed or Relapsed and Refractory Multiple Myeloma
Authors: San-Miguel Jesús F. , Richardson Paul G. , Günther Andreas , Sezer Orhan , Siegel David , Bladé Joan , LeBlanc Richard , Sutherland Heather , Sopala Monika , Mishra Kaushal K. , Mu Song , Bourquelot Priscille M. , Victoria Mateos María , Anderson Kenneth C.
Published: September 2013

Purpose

Despite advancements, prognosis for patients with relapsed/refractory multiple myeloma (MM) is poor, and novel therapies are needed. Panobinostat is a potent deacetylase inhibitor that elicits synergistic effects on MM cells in combination with bortezomib. This phase Ib study sought to determine the maximum-tolerated dose (MTD) of panobinostat plus bortezomib in patients with relapsed or relapsed and refractory MM.

Patients and Methods

In the dose-escalation phase (n = 47), panobinostat was administered orally thrice weekly every week in combination with bortezomib (21-day cycles). After MTD determination, patients were evaluated in an expansion phase (n = 15) that incorporated a 1-week treatment holiday of panobinostat, with dexamethasone added in cycle 2. Additional assessments included safety, pharmacokinetics, and efficacy per International Myeloma Working Group criteria.

Results

The MTD was established at panobinostat 20 mg plus bortezomib 1.3 mg/m2. Grade 3 or 4 adverse events (AEs) included thrombocytopenia (85.1%), neutropenia (63.8%), and asthenia (29.8%) in the escalation phase, and thrombocytopenia (66.7%), neutropenia (46.7%), and fatigue (20.0%) in the expansion phase. At MTD in the escalation phase, eight patients (47.1%) discontinued therapy as a result of AEs, whereas five patients (33.3%) discontinued treatment in the expansion phase. Expansion phase patients demonstrated greater median treatment duration. Overall response rate (ORR) was 73.3% in the expansion phase and 52.9% at the escalation phase MTD. Among bortezomib-refractory patients, the ORR was 26.3%, and 42.1% of patients had ≥ minimal response.

Conclusion

The MTD of panobinostat plus bortezomib was determined and demonstrated activity in patients with relapsed or relapsed/refractory MM, including bortezomib-refractory patients. A phase II/III clinical trial program (Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma [PANORAMA]) has been initiated.
Tivozanib Versus Sorafenib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma: Results From a Phase III Trial
Authors: Motzer Robert J. , Nosov Dmitry , Eisen Timothy , Bondarenko Igor , Lesovoy Vladimir , Lipatov Oleg , Tomczak Piotr , Lyulko Oleksiy , Alyasova Anna , Harza Mihai , Kogan Mikhail , Alekseev Boris Y. , Sternberg Cora N. , Szczylik Cezary , Cella David , Ivanescu Cristina , Krivoshik Andrew , Strahs Andrew , Esteves Brooke , Berkenblit Anna , Hutson Thomas E.
Published: September 2013

Purpose

Tivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR1), -2, and -3. This phase III trial compared tivozanib with sorafenib as initial targeted therapy in patients with metastatic renal cell carcinoma (RCC).

Patients and Methods

Patients with metastatic RCC, with a clear cell component, prior nephrectomy, measurable disease, and 0 or 1 prior therapies for metastatic RCC were randomly assigned to tivozanib or sorafenib. Prior VEGF-targeted therapy and mammalian target of rapamycin inhibitor were not permitted. The primary end point was progression-free survival (PFS) by independent review.

Results

A total of 517 patients were randomly assigned to tivozanib (n = 260) or sorafenib (n = 257). PFS was longer with tivozanib than with sorafenib in the overall population (median, 11.9 v 9.1 months; hazard ratio [HR], 0.797; 95% CI, 0.639 to 0.993; P = .042). One hundred fifty-six patients (61%) who progressed on sorafenib crossed over to receive tivozanib. The final overall survival (OS) analysis showed a trend toward longer survival on the sorafenib arm than on the tivozanib arm (median, 29.3 v 28.8 months; HR, 1.245; 95% CI, 0.954 to 1.624; P = .105). Adverse events (AEs) more common with tivozanib than with sorafenib were hypertension (44% v 34%) and dysphonia (21% v 5%). AEs more common with sorafenib than with tivozanib were hand-foot skin reaction (54% v 14%) and diarrhea (33% v 23%).

Conclusion

Tivozanib demonstrated improved PFS, but not OS, and a differentiated safety profile, compared with sorafenib, as initial targeted therapy for metastatic RCC.
Adjuvant Ganglioside GM2-KLH/QS-21 Vaccination Versus Observation After Resection of Primary Tumor > 1.5 mm in Patients With Stage II Melanoma: Results of the EORTC 18961 Randomized Phase III Trial
Authors: Eggermont Alexander M.M. , Suciu Stefan , Rutkowski Piotr , Marsden Jeremy , Santinami Mario , Corrie Philippa , Aamdal Steinar , Ascierto Paolo A. , Patel Poulam M. , Kruit Wim H. , Bastholt Lars , Borgognoni Lorenzo , Bernengo Maria Grazia , Davidson Neville , Polders Larissa , Praet Michel , Spatz Alan
Published: September 2013

Purpose

The GM2 ganglioside is an antigen expressed in the majority of melanomas. The GM2-KLH/QS-21 vaccine induces high immunoglobulin M (IgM) and IgG antibody responses. The EORTC 18961 trial compared the efficacy of GM2-KLH/QS-21 vaccination versus observation.

Patients and Methods

A total of 1,314 patients with a primary tumor > 1.50 mm in thickness (T3-4N0M0; American Joint Committee on Cancer stage II) were randomly assigned to GM2-KLH/QS-21 vaccination (n = 657) or observation (n = 657). Treatment consisted of subcutaneous injections once per week from week 1 to 4, then every 3 months for the first 2 years and every 6 months during the third year. Primary end point was relapse-free survival (RFS). Secondary end points were distant metastasis-free survival (DMFS) and overall survival (OS). Analyses were by intent to treat.

Results

After a median follow-up of 1.8 years, the trial was stopped at the second interim analysis for futility regarding RFS (hazard ratio [HR], 1.00; P = .99) and detrimental outcome regarding OS (HR, 1.66; P = .02). After a median follow-up of 4.2 years, we had recorded 400 relapses, nine deaths without relapse, a total of 236 deaths. At 4 years, the vaccination arm showed a decreased RFS rate of 1.2% (HR, 1.03; 95% CI, 0.84 to 1.25) and OS rate of 2.1% (HR, 1.16; 95% CI, 0.90 to 1.51). Toxicity was acceptable, with 4.6% of patients ending study participation because of toxicity.

Conclusion

GM2-KLH/QS-21 vaccination does not improve outcome for patients with stage II melanoma.
Long-Term Outcomes After Pelvic Radiation for Early-Stage Endometrial Cancer
Authors: Onsrud Mathias , Cvancarova Milada , Hellebust Taran P. , Tropé Claes G. , Kristensen Gunnar B. , Lindemann Kristina
Published: September 2013

Purpose

This follow-up of a randomized study was conducted to assess the long-term effects of external beam radiation therapy (EBRT) in the adjuvant treatment of early-stage endometrial cancer.

Patients and Methods

Between 1968 and 1974, 568 patients with stage I endometrial cancer were included. After primary surgery, patients were randomly assigned to either vaginal radium brachytherapy followed by EBRT (n = 288) or brachytherapy alone (n = 280). Overall survival was analyzed by using the Kaplan-Meier method. A Cox proportional hazards model was used to estimate hazard ratios (HRs) with 95% CIs. We also conducted analyses stratified by age groups.

Results

After median 20.5 years (range, 0 to 43.4 years) of follow-up, no statistically significant difference was revealed in overall survival (P = .186) between treatment groups. However, women younger than age 60 years had significantly higher mortality rates after EBRT (HR, 1.36; 95% CI, 1.06 to 1.76) than the control group. The risk of secondary cancer increased after EBRT, especially in women younger than age 60 years (HR, 2.02; 95% CI, 1.30 to 3.15).

Conclusion

We observed no survival benefit of external pelvic radiation in early-stage endometrial carcinoma. In women younger than age 60 years, pelvic radiation decreased survival and increased the risk of secondary cancer. Adjuvant EBRT should be used with caution, especially in women with a long life expectancy.
Prognostic Impact of Deficient DNA Mismatch Repair in Patients With Stage III Colon Cancer From a Randomized Trial of FOLFOX-Based Adjuvant Chemotherapy
Authors: Sinicrope Frank A. , Mahoney Michelle R. , Smyrk Thomas C. , Thibodeau Stephen N. , Warren Robert S. , Bertagnolli Monica M. , Nelson Garth D. , Goldberg Richard M. , Sargent Daniel J. , Alberts Steven R.
Published: September 2013

Purpose

The association of deficient DNA mismatch repair (dMMR) with prognosis in patients with colon cancer treated with adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy remains unknown.

Patients and Methods

Resected, stage III colon carcinomas from patients (N = 2,686) randomly assigned to FOLFOX ± cetuximab (North Central Cancer Treatment Group N0147 trial) were analyzed for mismatch repair (MMR) protein expression and mutations in BRAFV600E(exon 15) and KRAS (codons 12 and 13). Association of biomarkers with disease-free survival (DFS) was determined using Cox models. A validation cohort (Cancer and Leukemia Group B 88903 trial) was used.

Results

dMMR was detected in 314 (12%) of 2,580 tumors, of which 49.3% and 10.6% had BRAFV600Eor KRAS mutations, respectively. MMR status was not prognostic overall (adjusted hazard ratio [HR], 0.82; 95% CI, 0.64 to 1.07; P = .14), yet significant interactions were found between MMR and primary tumor site (Pinteraction= .009) and lymph node category (N1 v N2; Pinteraction= .014). Favorable DFS was observed for dMMR versus proficient MMR proximal tumors (HR, 0.71; 95% CI, 0.53 to 0.94; P = .018) but not dMMR distal tumors (HR, 1.71; 95% CI, 0.99 to 2.95; P = .056), adjusting for mutations and covariates. Any survival benefit of dMMR was lost in N2 tumors. Mutations in BRAFV600E(HR, 1.37; 95% CI, 1.08 to 1.70; P = .009) or KRAS (HR, 1.44; 95% CI, 1.21 to 1.70; P < .001) were independently associated with worse DFS. The observed MMR by tumor site interaction was validated in an independent cohort of stage III colon cancers (Pinteraction= .037).

Conclusion

The prognostic impact of MMR depended on tumor site, and this interaction was validated in an independent cohort. Among dMMR cancers, proximal tumors had favorable outcome, whereas distal or N2 tumors had poor outcome. BRAF or KRAS mutations were independently associated with adverse outcome.
End Points and Trial Design in Geriatric Oncology Research: A Joint European Organisation for Research and Treatment of Cancer–Alliance for Clinical Trials in Oncology–International Society of Geriatric Oncology Position Article
Authors: Wildiers Hans , Mauer Murielle , Pallis Athanasios , Hurria Arti , Mohile Supriya G. , Luciani Andrea , Curigliano Giuseppe , Extermann Martine , Lichtman Stuart M. , Ballman Karla , Cohen Harvey Jay , Muss Hyman , Wedding Ulrich
Published: September 2013

Selecting the most appropriate end points for clinical trials is important to assess the value of new treatment strategies. Well-established end points for clinical research exist in oncology but may not be as relevant to the older cancer population because of competing risks of death and potentially increased impact of therapy on global functioning and quality of life. This article discusses specific clinical end points and their advantages and disadvantages for older individuals.

Randomized or single-arm phase II trials can provide insight into the range of efficacy and toxicity in older populations but ideally need to be confirmed in phase III trials, which are unfortunately often hindered by the severe heterogeneity of the older cancer population, difficulties with selection bias depending on inclusion criteria, physician perception, and barriers in willingness to participate. All clinical trials in oncology should be without an upper age limit to allow entry of eligible older adults. In settings where so-called standard therapy is not feasible, specific trials for older patients with cancer might be required, integrating meaningful measures of outcome. Not all questions can be answered in randomized clinical trials, and large observational cohort studies or registries within the community setting should be established (preferably in parallel to randomized trials) so that treatment patterns across different settings can be compared with impact on outcome. Obligatory integration of a comparable form of geriatric assessment is recommended in future studies, and regulatory organizations such as the European Medicines Agency and US Food and Drug Administration should require adequate collection of data on efficacy and toxicity of new drugs in fit and frail elderly subpopulations.
Sentinel Node Mapping for Gastric Cancer: A Prospective Multicenter Trial in Japan
Authors: Kitagawa Yuko , Takeuchi Hiroya , Takagi Yu , Natsugoe Shoji , Terashima Masanori , Murakami Nozomu , Fujimura Takashi , Tsujimoto Hironori , Hayashi Hideki , Yoshimizu Nobunari , Takagane Akinori , Mohri Yasuhiko , Nabeshima Kazuhito , Uenosono Yoshikazu , Kinami Shinichi , Sakamoto Junichi , Morita Satoshi , Aikou Takashi , Miwa Koichi , Kitajima Masaki
Published: September 2013

Purpose

Complicated gastric lymphatic drainage potentially undermines the utility of sentinel node (SN) biopsy in patients with gastric cancer. Encouraged by several favorable single-institution reports, we conducted a multicenter, single-arm, phase II study of SN mapping that used a standardized dual tracer endoscopic injection technique.

Patients and Methods

Patients with previously untreated cT1 or cT2 gastric adenocarcinomas < 4 cm in gross diameter were eligible for inclusion in this study. SN mapping was performed by using a standardized dual tracer endoscopic injection technique. Following biopsy of the identified SNs, mandatory comprehensive D2 or modified D2 gastrectomy was performed according to current Japanese Gastric Cancer Association guidelines.

Results

Among 433 patients who gave preoperative consent, 397 were deemed eligible on the basis of surgical findings. SN biopsy was performed in all patients, and the SN detection rate was 97.5% (387 of 397). Of 57 patients with lymph node metastasis by conventional hematoxylin and eosin staining, 93% (53 of 57) had positive SNs, and the accuracy of nodal evaluation for metastasis was 99% (383 of 387). Only four false-negative SN biopsies were observed, and pathologic analysis revealed that three of those biopsies were pT2 or tumors > 4 cm. We observed no serious adverse effects related to endoscopic tracer injection or the SN mapping procedure.

Conclusion

The endoscopic dual tracer method for SN biopsy was confirmed as safe and effective when applied to the superficial, relatively small gastric adenocarcinomas included in this study.
Chemical preparation, kinetics of thermal behavior and infrared studies of Pb3(P3O9)2.3H2O and Cd3(P3O9)2.14H2O
Authors: Kheireddine Aziz , Tridane Malika , Belaaouad Said
Published: September 2013

Chemical preparation, thermal behavior, kinetic and IR studies are given for the cyclotriphosphates Pb3(P3O9)2.3H2O and Cd3(P3O9)2.14H2O. The later cyclotriphosphates have never been studied except their crystallographic characterization and are stable in the conditions of temperature and pressure of our laboratory until 343K. The final products of the dehydration and calcination of Pb3(P3O9)2.3H2O and Cd3(P3O9)2.14H2O, under atmospheric pressure, are respectively their long chain polyphosphates, [Pb(PO3)2]âˆž and Î²[Cd(PO3)2]âˆž. The intermediate product of the dehydration of Cd3(P3O9)2.14H2O, under atmospheric pressure, is its long chain polyphosphate form Î±, Î±[Cd(PO3)2]ï‚¥. [Pb(PO3)2]âˆž and Î²[Cd(PO3)2]âˆž are stable until their melting points at respectively 946K and 1153K. Two different methods, Ozawa and KAS have been selected in order to study the kinetics of thermal behavior of the cyclotriphosphates Pb3(P3O9)2.3H2O and Cd3(P3O9)2.14H2O for the first time. The kinetic and thermodynamic features of the dehydration, of the cited cyclotriphosphates, were determined and discussed on the basis of their crystalline structure. [Pb(PO3)2]âˆž, Î±[Cd(PO3)2]ï‚¥ and Î²[Cd(PO3)2]ï‚¥ have many applications in industry such as corrosion inhibitors.
Promoting Self-Determination of Students Who Are Deaf or Hard of Hearing
Authors: Luckner John L. , Sebald Ann M.
Published: September 2013

Self-Determination is a combination of attitudes, knowledge, and skills that enables individuals to make choices and engage in goal-directed, self-regulated behavior. Research in special education has demonstrated the benefits of promoting self-determination in achieving positive adult outcomes. However, to date, very little has been written about self-determination as it relates to the education of students who are deaf or hard of hearing. This article provides an overview of self-determination, suggestions for instructional planning, and guidance on resources that can be used to gather additional information.
Increasing Children’s ASL Classifier Production: A Multicomponent Intervention
Authors: Beal-Alvarez Jennifer S. , Easterbrooks Susan R.
Published: September 2013

The Authors examined classifier production during narrative retells by 10 deaf and hard of hearing students in grades 2–4 at a day school for the deaf following a 6-week intervention of repeated viewings of stories in American Sign Language (ASL) paired with scripted teacher mediation. Classifier production, documented through a multiple-baseline-across-participants design, was followed by visual analysis and calculation of the percentage of non-overlapping data (). Following the intervention, most students increased specific elements within their classifier production during narrative retells of stories they had watched and showed improved performance from pre- to postintervention measures. Picture support and fading of teacher mediation during retells variably affected classifier production. The results suggest that students may benefit from tailored intervention, including repeated viewings of ASL models paired with teacher mediation and possibly picture support, to increase classifier production during narrative retells.