bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with low cure rate of tuberculosis in remote poor areas of Shaanxi Province, China: a case control study
Authors: Ai Xianqin , Men Ke , Guo Liujia , Zhang Tianhua , Zhao Yan , Sun Xiaolu , Zhang Hongwei , He Guangxue , van der Werf Marieke J , van den Hof Susan
Published: March 2010

Background

The directly observed therapy-short course (DOTS) strategy was introduced in Shaanxi province, China to improve tuberculosis (TB) control by means of improved case detection (target: > = 70%) and treatment success rates (target: > = 85%) in new smear positive (SS+) TB patients. At a provincial level the targets were both reached in 2005. However in 30 (28%) out of 107 counties of Shaanxi province the cure rate was below 85%. This study aimed to investigate patient and treatment characteristics associated with non-cure after tuberculosis (TB) treatment in these counties.

Methods

In this case-control study, new smear positive TB cases in 30 counties with a cure rate <85% were included. Cured patients were compared to non-cured patients using logistic regression analysis to assess determinants for non-cure.

Results

Of the 659 patients included, 153 (23.2%) did not have cure as treatment outcome. Interruption of treatment was most strongly associated with non-cure (OR = 8.7, 95% CI 3.9-18.4). Other independent risk factors were co-morbidity, low education level, lack of appetite as an initial symptom of TB disease, diagnosis of TB outside of the government TB control institutes, missing sputum re-examinations during treatment, and not having a treatment observer. Twenty-six percent of patients did not have a treatment observer. The non-cure rate was better for those with a doctor (odds ratio (OR) 0.38, 95% confidence interval (CI) 0.17-0.88) as treatment observer than for those with a family member (OR 0.62, 95%CI 0.37-1.03). The main reason for interrupted treatment mentioned by patients was presence of adverse effects during treatment (46.5%).

Conclusions

Interruption of treatment was most strongly associated with non-cure. Although treatment observation by medical staff is preferred, in order to diminish the proportion of patients who do not have a treatment observer and thereby reduce the proportion of patients who interrupt treatment, we suggest making it possible for family members, after sufficient training, to be treatment observers in remote areas where it is logistically difficult to have village doctors observe treatment for all patients.
Evaluation of different expression systems for the heterologous expression of pyranose 2-oxidase from Trametes multicolor in E. coli
Authors: Spadiut Oliver , Posch Gerald , Ludwig Roland , Haltrich Dietmar , Peterbauer Clemens K
Published: March 2010

The heterologous production of the industrially relevant fungal enzyme pyranose 2-oxidase in the prokaryotic host E. coli was investigated using 3 different expression systems, i.e. the well-studied T7 RNA polymerase based pET21d+, the L-arabinose inducible pBAD and the pCOLD system. Preliminary experiments were done in shaking flasks at 25°C and optimized induction conditions to compare the productivity levels of the different expression systems. The pET21d+ and the pCOLD system gave 29 U/L·h and 14 U/L·h of active pyranose 2-oxidase, respectively, whereas the pBAD system only produced 6 U/L·h. Process conditions for batch fermentations were optimized for the pET21d+ and the pCOLD systems in order to reduce the formation of inactive inclusion bodies. The highest productivity rate with the pET21d+ expression system in batch fermentations was determined at 25°C with 32 U/L·h. The pCOLD system showed the highest productivity rate (19 U/L·h) at 25°C and induction from the start of the cultivation. Using the pCOLD system in a fed batch fermentation at 25°C with a specific growth rate of μ = 0.15 h-1resulted in the highest productivity rate of active pyranose oxidase with 206 U/L·h.
The infectivity of the entomopathogenic fungus Beauveria bassiana to insecticide-resistant and susceptible Anopheles arabiensis mosquitoes at two different temperatures
Authors: Kikankie Christophe K , Brooke Basil D , Knols Bart GJ , Koekemoer Lizette L , Farenhorst Marit , Hunt Richard H , Thomas Matthew B , Coetzee Maureen
Published: March 2010

Background

Control of the major African malaria vector species continues to rely extensively on the application of residual insecticides through indoor house spraying or bed net impregnation. Insecticide resistance is undermining the sustainability of these control strategies. Alternatives to the currently available conventional chemical insecticides are, therefore, urgently needed. Use of fungal pathogens as biopesticides is one such possibility. However, one of the challenges to the approach is the potential influence of varied environmental conditions and target species that could affect the efficacy of a biological 'active ingredient'. An initial investigation into this was carried out to assess the susceptibility of insecticide-susceptible and resistant laboratory strains and wild-collectedAnopheles arabiensismosquitoes to infection with the fungusBeauveria bassianaunder two different laboratory temperature regimes.

Methods

Insecticide susceptibility to all four classes of insecticides recommended by WHO for vector control was tested on laboratory and wild-caughtAn. arabiensis, using standard WHO bioassay protocols. Mosquito susceptibility to fungus infection was tested using dry spores ofB. bassianaunder two temperature regimes (21 ± 1°C or 25 ± 2°C) representative of indoor conditions observed in western Kenya. Cox regression analysis was used to assess the effect of fungal infection on mosquito survival and the effect of insecticide resistance status and temperature on mortality rates following fungus infection.

Results

Survival data showed no relationship between insecticide susceptibility and susceptibility toB. bassiana. All tested colonies showed complete susceptibility to fungal infection despite some showing high resistance levels to chemical insecticides. There was, however, a difference in fungus-induced mortality rates between temperature treatments with virulence significantly higher at 25°C than 21°C. Even so, because malaria parasite development is also known to slow as temperatures fall, expected reductions in malaria transmission potential due to fungal infection under the cooler conditions would still be high.

Conclusions

These results provide evidence that the entomopathogenic fungusB. bassianahas potential for use as an alternative vector control tool against insecticide-resistant mosquitoes under conditions typical of indoor resting environments. Nonetheless, the observed variation in effective virulence reveals the need for further study to optimize selection of isolates, dose and use strategy in different eco-epidemiological settings.
Dietary saponins of sea cucumber alleviate orotic acid-induced fatty liver in rats via PPARα and SREBP-1c signaling
Authors: Hu Xiao-Qian , Wang Yu-Ming , Wang Jing-Feng , Xue Yong , Li Zhao-Jie , Nagao Koji , Yanagita Teruyoshi , Xue Chang-Hu
Published: March 2010

Background

Nonalcoholic fatty liver disease is the most common chronic liver disease in the world, and is becoming increasingly prevalent. Saponins of sea cucumber (SSC) are proven to exhibit various biological activities. Therefore, the present study was undertaken to examine the effect of saponins extracted from sea cucumber (Pearsonothuria graeffei) on the preventive activity of fatty liver in rats.

Methods

Male Wistar rats were randomly divided into five groups, including normal control group, fatty liver model group, SSC-treated group with SSC at levels of 0.01%, 0.03% and 0.05%. Model rats were established by administration with 1% orotic acid (OA). After the experiment period, serum total cholesterol (TC), triglyceride (TG), and hepatic lipid concentrations were determined. To search for a possible mechanism, we examined the changes of key enzymes and transcriptional factors involved in hepatic lipids biosynthesis, fatty acid β-oxidation.

Results

Both 0.03% and 0.05% SSC treatment alleviated hepatic steatosis and reduced serum TG and TC concentration significantly in OA fed rats. Hepatic lipogenic enzymes, such as fatty acid synthase (FAS), malic enzyme (ME), and glucose-6-phosphate dehydrogenase (G6PDH) activities were inhibited by SSC treatment. SSC also decreased the gene expression of FAS, ME, G6PDH and sterol-regulatory element binding protein (SREBP-1c). Otherwise, the rats feeding with SSC showed increased carnitine palmitoyl transferase (CPT) activity in the liver. Hepatic peroxisome proliferator-activated receptor (PPARα), together with its target gene CPT and acyl-CoA oxidase (ACO) mRNA expression were also upregulated by SSC.

Conclusions

According to our study, the lipids-lowering effect of dietary SSC may be partly associated with the enhancement of β-oxidation via PPARα activation. In addition, the inhibited SREBP-1c- mediated lipogenesis caused by SSC may also contribute to alleviating fatty liver.
Methamphetamine use and malnutrition among street-involved youth
Authors: Werb Dan , Kerr Thomas , Zhang Ruth , Montaner Julio SG , Wood Evan
Published: March 2010

We sought to explore the effect of crystal methamphetamine use on the risk of experiencing malnutrition among street-involved youth in Vancouver, Canada. Risk of malnutrition was defined as being hungry but not having enough money to buy food. Socio-demographic and drug use factors associated with risk of malnutrition were investigated using univariate and multivariate analysis among a prospective cohort of street-involved youth known as the At-Risk Youth Study (ARYS). Between September 2005 and December 2006, 509 street-involved youth were enrolled in ARYS, among whom 21% reported being at risk of malnutrition as defined above in the previous six months. In multivariate analysis, only non-injection crystal methamphetamine was significantly associated with being at risk of malnutrition among this cohort (Adjusted Odds Ratio [AOR] = 1.60, 95% Confidence Interval [CI]: 1.03 - 2.48, p = 0.036). Interventions seeking to address food insecurity among street youth may benefit from considering drug use patterns since methamphetamine use predicted higher risk in this setting.
Prognostic impact of ZAP-70 expression in chronic lymphocytic leukemia: mean fluorescence intensity T/B ratio versus percentage of positive cells
Authors: Rossi Francesca M , Del Principe Maria Ilaria , Rossi Davide , Irno Consalvo Maria , Luciano Fabrizio , Zucchetto Antonella , Bulian Pietro , Bomben Riccardo , Dal Bo Michele , Fangazio Marco , Benedetti Dania , Degan Massimo , Gaidano Gianluca , Del Poeta Giovanni , Gattei Valter
Published: March 2010

Background

ZAP-70 is an independent negative prognostic marker in chronic lymphocytic leukemia (CLL). Usually, its expression is investigated by flow cytometric protocols in which the percentage of ZAP-70 positive CLL cells is determined in respect to isotypic control (ISO-method) or residual ZAP-70 positive T cells (T-method). These methods, however, beside suffering of an inherent subjectivity in their application, may give discordant results in some cases. The aim of this study was to assess the prognostic significance of these methods in comparison with another in which ZAP-70 expression was evaluated as a Mean-Fluorescence-Intensity Ratio between gated T and CLL cells (T/B Ratio-method).

Methods

Cytometric files relative to ZAP-70 determination according to the three readouts were retrospectively reviewed on a cohort of 173 patients (test set), all with complete clinical and biological prognostic assessment and time-to-treatment (TTT) available. Findings were then validated in an independent cohort of 341 cases from a different institution (validation set).

Results

The optimal prognostic cut-offs for ZAP-70 expression were selected at 11% (ISO-method) or 20% of positive cells (T-method), as well as at 3.0 (T/B Ratio-method) in the test set; these cut-offs yielded 66, 60 and 73 ZAP-70+ cases, respectively. Univariate analyses resulted in a better separation of ZAP-70+ vs. ZAP-70- CLL patients utilizing the T/B Ratio, compared to T- or ISO-methods. In multivariate analyses which included the major clinical and biological prognostic markers for CLL, the prognostic impact of ZAP-70 appeared stronger when the T/B-Ratio method was applied. These findings were confirmed in the validation set, in which ZAP-70 expression, evaluated by the T- (cut-off = 20%) or T/B Ratio- (cut-off = 3.0) methods, yielded 180 or 127 ZAP-70+ cases, respectively. ZAP-70+ patients according to the T/B Ratio-method had shorter TTT, both if compared to ZAP-70- CLL, and to cases classified ZAP-70+ by the T-method only.

Conclusions

We suggest to evaluate ZAP-70 expression in routine settings using the T/B Ratio-method, given the operator and laboratory independent feature of this approach. We propose the 3.0 T/B Ratio value as optimal cut-off to discriminate ZAP-70+ (T/B Ratio less than 3.0) from ZAP-70- (T/B Ratio more/equal than 3.0) cases.
The Nordic Maintenance Care Program - Time intervals between treatments of patients with low back pain: how close and who decides?
Authors: Sandnes Kjerstin F , Bjørnstad Charlotte , Leboeuf-Yde Charlotte , Hestbaek Lise
Published: March 2010

Background

The management of chiropractic patients with acute and chronic/persistent conditions probably differs. However, little is known on this subject. There is, for example, a dearth of information on maintenance care (MC). Thus it is not known if patients on MC are coerced to partake in a program of frequent treatments over a long period of time, or if they are actively involved in designing their own individualized treatment program.

Objectives

It was the purpose of this study to investigate how chiropractic patients with low back pain were scheduled for treatment, with special emphasis on MC. The specific research questions were: 1. How many patients are on maintenance care? 2) Are there specific patterns of intervals between treatments for patients and, if so, do they differ between MC patients and non-MC patients? 3. Who decides on the next treatment, the patient, the chiropractor or both, and are there any differences between MC patients and non-MC patients?

Methods

Chiropractic students, who during their summer holidays were observers in chiropractic clinics in Norway and Denmark, recorded whether patients were classified by the treating chiropractor as a MC-patient or not, dates for last and subsequent visits, and made a judgement on whether the patient or the chiropractor decided on the next appointment.

Results

Observers in the study were 16 out of 30 available students. They collected data on 868 patients from 15 Danish and 13 Norwegian chiropractors. Twenty-two percent and 26%, respectively, were classified as MC patients. Non-MC patients were most frequently seen within 1 week. For MC patients, the previous visit was most often 2-4 weeks prior to the actual visit, and the next appointment between 1 and 3 months. This indicates a gradual increase in intervals. The decision of the next visit was mainly made by the chiropractor, also for MC patients. However, the study samples of chiropractors appear not to be representative of the general Danish and Norwegian chiropractic profession and the patients may also have been non-representative.

Conclusion

There were two distinctly different patterns for the time period between visits for MC patients and non-MC patients. For non-MC patients, the most frequent interval between visits was one week and for MC patients, the period was typically between two weeks and three months. It was primarily the chiropractor who made the next visit-decision. However, these results can perhaps not be extrapolated to other groups of patients and chiropractors.
Endovascular treatment of a Superior Mesenteric Artery Syndrome variant secondary to traumatic pseudoaneurysm
Authors: Au-Yong Iain , Watson Nicholas FS , Boereboom Catherine L , Bowling Timothy E , Abercrombie John F , Whitaker Simon C
Published: March 2010

Pseudoaneurysms related to the superior mesenteric artery (SMA) are a recognised complication of trauma to the vessel, and successful treatment with stenting has been previously described. We report the case of a patient who presented with obstruction of the fourth part of the duodenum secondary to a traumatic pseudoaneurysm, a hitherto unreported variant of superior mesenteric artery syndrome. Exclusion of the pseudoaneurysm and relief of the duodenal obstruction were simultaneously achieved by placement of a covered stent.
Challenges faced by health workers in providing counselling services to HIV‐positive children in Uganda: a descriptive study
Authors: Rujumba Joseph , Mbasaalaki‐Mwaka Cissy L , Ndeezi Grace
Published: March 2010

Background

The delivery of HIV counselling and testing services for children remains an uphill task for many health workers in HIV‐endemic countries, including Uganda. We conducted a descriptive study to explore the challenges of providing HIV counselling and testing services to children in Uganda.

Methods

A descriptive study was conducted in the districts of Kampala and Kabarole in Uganda. The data were collected using semi‐structured individual interviews and focus group discussions with health workers who are involved in the care of HIV‐positive children. Key informant interviews were conducted with the administrators of the 10 study healthcare institutions. Quantitative data were summarized using frequency tables, while qualitative data were analyzed using the content thematic approach.

Results

Counselling children was reported to be a difficult exercise due to some children being unable to express themselves, being dependent on adults for their care, being fearful, and requiring more time to open up during counselling. This was compounded by some caretakers' unwillingness and difficulty to disclose the HIV status of their children. Other issues about the caretakers were: lack of consistency in caretakers; old age; sickness; and poverty. Health workers mentioned the following as some of the challenges they face in the delivery of HIV counselling and testing services for children: lack of counselling skills; failure to cope with the knowledge demand; difficulty to facilitate disclosure; heavy work load; and lack of other support services. Institutions were found to be constrained by limited space and lack of antiretrovirals for children.

Conclusions

The major challenges in the delivery of paediatric HIV services were related to the knowledge gap in paediatric HIV and the lack of counselling skills, as well as health system‐related constraints. There is a need to train health workers in child‐counselling skills, especially in the issues of disclosure, sexuality and sexual abuse, as well as in addressing fears related to death and an uncertain future, in order to improve paediatric HIV care. Provision of child‐friendly services, guidelines and antiretroviral formulations for children may provide a window of hope to improve HIV counselling and testing services for children.
Circulating surfactant protein -D is low and correlates negatively with systemic inflammation in early, untreated rheumatoid arthritis
Authors: Christensen Anne Friesgaard , Sørensen Grith Lykke , Hørslev-Petersen Kim , Holmskov Uffe , Lindegaard Hanne Merete , Junker Kirsten , Hetland Merete Lund , Stengaard-Pedersen Kristian , Jacobsen Søren , Lottenburger Tine , Ellingsen Torkell , Andersen Lis Smedegaard , Hansen Ib , Skjødt Henrik , Pedersen Jens Kristian , Lauridsen Ulrik Birk , Svendsen Anders , Tarp Ulrik , Pødenphant Jan , Vestergaard Aage , Jurik Anne Grethe , Østergaard Mikkel , Junker Peter
Published: March 2010

Introduction

Surfactant protein D (SP-D) is a collectin with immuno-regulatory functions, which may depend on oligomerization. Anti-microbial and anti-inflammatory properties have been attributed to multimeric SP-D variants, while trimeric subunits per se have been suggested to enhance inflammation. Previously, we reported low circulating SP-D in early rheumatoid arthritis (RA), and the present investigation aims to extend these data by serial SP-D serum measurements, studies on synovial fluid, SP-D size distribution and genotyping in patients with early RA.

Methods

One-hundred-and-sixty disease-modifying antirheumatic drug (DMARD) naïve RA patients with disease duration less than six months were studied prospectively for four years (CIMESTRA (Ciclosporine, Methotrexate, Steroid in RA) trial) including disease activity measures (C-reactive protein, joint counts and Health Assessment Questionnaire (HAQ) score), autoantibodies, x-ray findings and SP-D. SP-D was quantified by enzyme-linked immunosorbent assay (ELISA) and molecular size distribution was assessed by gel filtration chromatography. Further, SP-D Met11Thr single nucleotide polymorphism (SNP) analysis was performed.

Results

Serum SP-D was significantly lower in RA patients at baseline compared with healthy controls (P < 0.001). SP-D increased slightly during follow-up (P < 0.001), but was still subnormal at four years after adjustment for confounders (P < 0.001). SP-D in synovial fluid was up to 2.5-fold lower than in serum. While multimeric variants were detected in serum, SP-D in synovial fluid comprised trimeric subunits only. There were no significant associations between genotype distribution and SP-D. Baseline SP-D was inversely associated to CRP and HAQ score. A similar relationship was observed regarding temporal changes in SP-D and CRP (zero to four years). SP-D was not associated to x-ray findings.

Conclusions

This study confirms that circulating SP-D is persistently subnormal in early and untreated RA despite a favourable therapeutic response obtained during four years of follow-up. SP-D correlated negatively to disease activity measures, but was not correlated with x-ray progression or SP-D genotype. These observations suggest that SP-D is implicated in RA pathogenesis at the protein level. The exclusive presence of trimeric SP-D in affected joints may contribute to the maintenance of joint inflammation.

Trial registration

(j.nr NCT00209859).
Automated evaluation of autoantibodies on human epithelial-2 cells as an approach to standardize cell-based immunofluorescence tests
Authors: Egerer Karl , Roggenbuck Dirk , Hiemann Rico , Weyer Max-Georg , Büttner Thomas , Radau Boris , Krause Rosemarie , Lehmann Barbara , Feist Eugen , Burmester Gerd-Rüdiger
Published: March 2010

Introduction

Analysis of autoantibodies (AAB) by indirect immunofluorescence (IIF) is a basic tool for the serological diagnosis of systemic rheumatic disorders. Automation of autoantibody IIF reading including pattern recognition may improve intra- and inter-laboratory variability and meet the demand for cost-effective assessment of large numbers of samples. Comparing automated and visual interpretation, the usefulness for routine laboratory diagnostics was investigated.

Methods

Autoantibody detection by IIF on human epithelial-2 (HEp-2) cells was conducted in a total of 1222 consecutive sera of patients with suspected systemic rheumatic diseases from a university routine laboratory (n = 924) and a private referral laboratory (n = 298). IIF results from routine diagnostics were compared with a novel automated interpretation system.

Results

Both diagnostic procedures showed a very good agreement in detecting AAB (kappa = 0.828) and differentiating respective immunofluorescence patterns. Only 98 (8.0%) of 1222 sera demonstrated discrepant results in the differentiation of positive from negative samples. The contingency coefficients of chi-square statistics were 0.646 for the university laboratory cohort with an agreement of 93.0% and 0.695 for the private laboratory cohort with an agreement of 90.6%, P < 0.0001, respectively. Comparing immunofluorescence patterns, 111 (15.3%) sera yielded differing results.

Conclusions

Automated assessment of AAB by IIF on HEp-2 cells using an automated interpretation system is a reliable and robust method for positive/negative differentiation. Employing novel mathematical algorithms, automated interpretation provides reproducible detection of specific immunofluorescence patterns on HEp-2 cells. Automated interpretation can reduce drawbacks of IIF for AAB detection in routine diagnostics providing more reliable data for clinicians.
The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer
Authors: Hu Zhi , Huang Ge , Sadanandam Anguraj , Gu Shenda , Lenburg Marc E , Pai Melody , Bayani Nora , Blakely Eleanor A , Gray Joe W , Mao Jian-Hua
Published: March 2010

Introduction

HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome.

Methods

We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis.

Results

HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression were validated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis than those with low levels. Knock down of HJURP in human breast cancer cells using shRNA reduced the sensitivity to radiation treatment. HJURP mRNA levels were significantly correlated with CENPA mRNA levels.

Conclusions

HJURP mRNA level is a prognostic factor for disease-free and overall survival in patients with breast cancer and is a predictive biomarker for sensitivity to radiotherapy.
Identification and analysis of unitary pseudogenes: historic and contemporary gene losses in humans and other primates
Authors: Zhang Zhengdong D , Frankish Adam , Hunt Toby , Harrow Jennifer , Gerstein Mark
Published: March 2010

Background

Unitary pseudogenes are a class of unprocessed pseudogenes without functioning counterparts in the genome. They constitute only a small fraction of annotated pseudogenes in the human genome. However, as they represent distinct functional losses over time, they shed light on the unique features of humans in primate evolution.

Results

We have developed a pipeline to detect human unitary pseudogenes through analyzing the global inventory of orthologs between the human genome and its mammalian relatives. We focus on gene losses along the human lineage after the divergence from rodents about 75 million years ago. In total, we identify 76 unitary pseudogenes, including previously annotated ones, and many novel ones. By comparing each of these to its functioning ortholog in other mammals, we can approximately date the creation of each unitary pseudogene (that is, the gene 'death date') and show that for our group of 76, the functional genes appear to be disabled at a fairly uniform rate throughout primate evolution - not all at once, correlated, for instance, with the 'Alu burst'. Furthermore, we identify 11 unitary pseudogenes that are polymorphic - that is, they have both nonfunctional and functional alleles currently segregating in the human population. Comparing them with their orthologs in other primates, we find that two of them are in fact pseudogenes in non-human primates, suggesting that they represent cases of a gene being resurrected in the human lineage.

Conclusions

This analysis of unitary pseudogenes provides insights into the evolutionary constraints faced by different organisms and the timescales of functional gene loss in humans.
Acquisition footprints and seafloor coupling in multicomponent OBC seismic data
Authors: Brown R. James
Published: March 2010

In four-component (4-C) towed ocean-bottom-cable (OBC) data sets, acquisition footprints are often observed. Sometimes these exhibit a spatial period equal to the length of the receiver cable. I have analyzed a 2D 4-C OBC data set, looking at common-offset gathers (COG), spectral analyses, and hodogram analyses of the direct P-wave first breaks. The acquisition footprint is seen to be directly related to the following effects observed on a few of the multicomponent receivers, namely, those nearest to the towing vessel: significant delays on the inline component though not on the downgoing direct-P first breaks; depletion of higher frequencies (narrower bandwidth) on the inline component; and oscillatory motion closer to the vertical on the direct-P first breaks equivalent to decreased amplitude on the in-line component. This is interpreted to be a result of the towing procedure wherein the leading end of the cable, with the first few receiver modules, is raised from the seafloor and laid down again, relatively lightly, on top of seafloor material that might be poorly consolidated, while the trailing receivers are pulled through and down into this material. For these leading receiver modules, this results in poor inline horizontal coupling (i.e., slipping) and delayed P-S onsets due to their vertically higher positions (relative to the trailing receivers) and quite high near-seafloor [Formula: see text] ratios. To rectify this problem in future acquisition, a longer lead-in cable should prevent lifting of the leading receivers and allow all of them to couple with the seafloor in the same way. For data already acquired with an acquisition footprint on the inline component, a two-step process involving surface-consistent deconvolution or trace equalization and static correction is proposed.
3D stochastic inversion of gravity data using cokriging and cosimulation
Authors: Shamsipour Pejman , Marcotte Denis , Chouteau Michel , Keating Pierre
Published: March 2010

A new application has been developed, based on geostatistical techniques of cokriging and conditional simulation, for the 3D inversion of gravity data including geologic constraints. The necessary gravity, density, and gravity-density covariance matrices are estimated using the observed gravity data. Then the densities are cokriged or simulated using the gravity data as the secondary variable. The model allows noise to be included in the observations. The method is applied to two synthetic models: a short dipping dike and a stochastic distribution of densities. Then some geologic information is added as constraints to the cokriging system. The results show the ability of the method to integrate complex a priori information. The survey data of the Matagami mining camp are considered as a case study. The inversion method based on cokriging is applied to the residual anomaly to map the geology through the estimation of the density distribution in this region. The results of the inversion and simulation methods are in good agreement with the surface geology of the survey region.
It's a matter of size: Magnitude and moment estimates for microseismic data
Authors: Shemeta Julie , Anderson Paul
Published: March 2010

Microseismic mapping is a valuable tool for assessing hydraulic fracture stimulations. During a stimulation treatment, borehole, near-surface, or surface geophones record passive seismic data. The microseismic events are thought to be shear failures that occur around the opening of a tensile hydraulic fracture as it grows. Over the past several years, there has been a large growth in the number of hydraulic fracture monitoring surveys, along with the number of vendors who acquire and process microseismic data. Here we discuss two attributes of microseismic data which are associated with the size of the passive event: seismic moment and magnitude.
Seismogenic index and magnitude probability of earthquakes induced during reservoir fluid stimulations
Authors: Shapiro Serge A. , Dinske Carsten , Langenbruch Cornelius , Wenzel Friedemann
Published: March 2010

An important characteristic of seismicity is the distribution of magnitudes of earthquakes. Fluid injection in rocks, aimed to create enhanced geothermal systems (EGS), can sometimes produce significant seismic events (e.g., Majer et al., 2007). This is rarely the case in hydraulic fracturing of hydrocarbon reservoirs. However, in any case the behavior of the seismicity triggering in space and in time is controlled by the process of stress relaxation and pore-pressure perturbation that was initially created at the injection source. This relaxation process can be approximated by pressure diffusion (possibly a nonlinear one) in the pore fluid of rocks (e.g., Shapiro and Dinske, 2009). At some locations the tectonic stress in the Earth's crust is close to a critical stress, causing brittle failure of rocks. Increasing fluid pressure in such a reservoir causes pressure in the connected pore and fracture space of rocks to increase. Such an increase in the pore pressure consequently causes a decrease of the effective normal stress. This leads to sliding along pre-existing, favorably oriented, subcritical cracks.
Moderate-to-large seismicity induced by hydrocarbon production
Authors: Suckale Jenny
Published: March 2010

It is well known that various human activities have the potential to generate seismic activity. Examples range from subsurface waste injection and reservoir impoundment in the vicinity of large dams to the development of mining, geothermal or hydrocarbon resources. Recently, induced seismicity in connection to geologic carbon sequestration projects has emerged as a new field of interest. This review discusses seismicity induced by hydrocarbon production. In particular, I focus on published cases for which earthquakes of moderate-to-large magnitudes-in other words earthquakes that can be felt on the surface-have been reported. I also discuss current theoretical approaches to model this phenomenon. The emphasis on moderate-to-large magnitudes is intended to complement the other contributions in this issue which focus primarily on microseismicity. Evidently, it is important to understand the conditions under which hydrocarbon production may induce seismic activity in order to ensure that field operations can be performed safely.
Microseismic: Growth born from success
Authors: Maxwell Shawn
Published: March 2010

Over the last several years, microseismic (MS) monitoring has quickly grown as a technology to map various reservoir processes. Imaging hydraulic fracture stimulations is the most common application especially within North America. As indicated in the introduction to this special section, initial interest in MS was primarily in the engineering community. As the method was pushed forward by the engineers, geophysicists within operating companies began to get pulled in to support the engineering projects. As application of the method gathered steam, interest expanded in the geophysical community and into academia as seen by the growth of research consortia looking at the technique. While MS is a seismic technique, it is sufficiently novel that most geophysicists are largely uninformed about technology challenges. Nevertheless, over the last few years the geophysical community has been both educating itself and taking stewardship of the technology. MS remains a unique geophysical technology although the technology was originally adopted by engineers.
GEOPHYSICS BRIGHT SPOTS
Authors: Mahrer Ken
Published: March 2010

As our history shows, GEOPHYSICS has published and continues to publish articles on the breadth of sub-Earth-surface investigations. From the January-February issue, we highlight a few. Consider this your invitation to make the time and give these and their sister articles their due.
Review of Adherence-Related Issues in Adolescents and Young Adults With Cancer
Authors: Butow Phyllis , Palmer Susan , Pai Ahna , Goodenough Belinda , Luckett Tim , King Madeleine
Published: March 2010

Purpose

This review aims to provide a broad overview of the issues and clinical challenges of nonadherence in adolescents and young adults (AYAs) with cancer. Nonadherence can reduce treatment efficacy, which places the patient at higher risk of relapse, adverse effects, and poor outcomes.

Design

A review of the English-speaking literature between 1980 and 2008 was conducted to identify relevant publications, which were supplemented by reference and author searches.

Results

Definition and measurement of adherence varies. Most studies have not clearly delineated an AYA age group (ie, 15-25 years) and have been dominated by leukemia and lymphoma samples. Estimates for nonadherence in this population range from 27% to 60%, with openness of family relationships and support found to predict adherence. Strategies to avoid, assess, and manage nonadherence are presented.

Conclusion

Overall, the evidence base for adherence and strategies to promote it in AYAs with cancer is woefully lacking. There is a need for high-quality studies that target clinically important questions, randomized controlled trials of theoretically based interventions, and development and evaluation of training programs for oncology staff in the special issues faced by AYAs with cancer.
Pancreatic Proteolytic Enzyme Therapy Compared With Gemcitabine-Based Chemotherapy for the Treatment of Pancreatic Cancer
Authors: Chabot John A. , Tsai Wei-Yann , Fine Robert L. , Chen Chunxia , Kumah Carolyn K. , Antman Karen A. , Grann Victor R.
Published: March 2010

Purpose

Conventional medicine has had little to offer patients with inoperable pancreatic adenocarcinoma; thus, many patients seek alternative treatments. The National Cancer Institute, in 1998, sponsored a randomized, phase III, controlled trial of proteolytic enzyme therapy versus chemotherapy. Because most eligible patients refused random assignment, the trial was changed in 2001 to a controlled, observational study.

Methods

All patients were seen by one of the investigators at Columbia University, and patients who received enzyme therapy were seen by the participating alternative practitioner. Of 55 patients who had inoperable pancreatic cancer, 23 elected gemcitabine-based chemotherapy, and 32 elected enzyme treatment, which included pancreatic enzymes, nutritional supplements, detoxification, and an organic diet. Primary and secondary outcomes were overall survival and quality of life, respectively.

Results

At enrollment, the treatment groups had no statistically significant differences in patient characteristics, pathology, quality of life, or clinically meaningful laboratory values. Kaplan-Meier analysis found a 9.7-month difference in median survival between the chemotherapy group (median survival, 14 months) and enzyme treatment groups (median survival, 4.3 months) and found an adjusted-mortality hazard ratio of the enzyme group compared with the chemotherapy group of 6.96 (P < .001). At 1 year, 56% of chemotherapy-group patients were alive, and 16% of enzyme-therapy patients were alive. The quality of life ratings were better in the chemotherapy group than in the enzyme-treated group (P < .01).

Conclusion

Among patients who have pancreatic cancer, those who chose gemcitabine-based chemotherapy survived more than three times as long (14.0 v 4.3 months) and had better quality of life than those who chose proteolytic enzyme treatment.
Are the Most Distressing Concerns of Patients With Inoperable Lung Cancer Adequately Assessed? A Mixed-Methods Analysis
Authors: Tishelman Carol , Lövgren Malin , Broberger Eva , Hamberg Katarina , Sprangers Mirjam A.G.
Published: March 2010

Purpose

Standardized questionnaires for patient-reported outcomes are generally composed of specified predetermined items, although other areas may also cause patients distress. We therefore studied reports of what was most distressing for 343 patients with inoperable lung cancer (LC) at six time points during the first year postdiagnosis and how these concerns were assessed by three quality-of-life and symptom questionnaires.

Patients and Methods

Qualitative analysis of patients' responses to the question “What do you find most distressing at present?” generated 20 categories, with 17 under the dimensions of “bodily distress,” “life situation with LC,” and “iatrogenic distress.” Descriptive and inferential statistical analyses were conducted.

Results

The majority of statements reported as most distressing related to somatic and psychosocial problems, with 26% of patients reporting an overarching form of distress instead of specific problems at some time point. Twenty-seven percent reported some facet of their contact with the health care system as causing them most distress. While 55% to 59% of concerns reported as most distressing were clearly assessed by the European Organisation for Research and Treatment for Cancer Quality of Life Questionnaire Core-30 and Lung Cancer Module instruments, the Memorial Symptom Assessment Scale, and the modified Distress Screening Tool, iatrogenic distress is not specifically targeted by any of the three instruments examined.

Conclusion

Using this approach, several distressing issues were found to be commonly reported by this patient group but were not assessed by standardized questionnaires. This highlights the need to carefully consider choice of instrument in relation to study objectives and characteristics of the sample investigated and to consider complementary means of assessment in clinical practice.
Prediction of Risk of Distant Recurrence Using the 21-Gene Recurrence Score in Node-Negative and Node-Positive Postmenopausal Patients With Breast Cancer Treated With Anastrozole or Tamoxifen: A TransATAC Study
Authors: Dowsett Mitch , Cuzick Jack , Wale Christopher , Forbes John , Mallon Elizabeth A. , Salter Janine , Quinn Emma , Dunbier Anita , Baum Michael , Buzdar Aman , Howell Anthony , Bugarini Roberto , Baehner Frederick L. , Shak Steven
Published: March 2010

Purpose

To determine whether the Recurrence Score (RS) provided independent information on risk of distant recurrence (DR) in the tamoxifen and anastrozole arms of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trial.

Patients and Methods

RNA was extracted from 1,372 tumor blocks from postmenopausal patients with hormone receptor–positive primary breast cancer in the monotherapy arms of ATAC. Twenty-one genes were assessed by quantitative reverse transcriptase polymerase chain reaction, and the RS was calculated. Cox proportional hazards models assessed the value of adding RS to a model with clinical variables (age, tumor size, grade, and treatment) in node-negative (N0) and node-positive (N+) women.

Results

Reportable scores were available from 1,231 evaluable patients (N0, n = 872; N+, n = 306; and node status unknown, n = 53); 72, 74, and six DRs occurred in N0, N+, and node status unknown patients, respectively. For both N0 and N+ patients, RS was significantly associated with time to DR in multivariate analyses (P < .001 for N0 and P = .002 for N+). RS also showed significant prognostic value beyond that provided by Adjuvant! Online (P < .001). Nine-year DR rates in low (RS < 18), intermediate (RS = 18 to 30), and high RS (RS ≥ 31) groups were 4%, 12%, and 25%, respectively, in N0 patients and 17%, 28%, and 49%, respectively, in N+ patients. The prognostic value of RS was similar in anastrozole- and tamoxifen-treated patients.

Conclusion

This study confirmed the performance of RS in postmenopausal HR+ patients treated with tamoxifen in a large contemporary population and demonstrated that RS is an independent predictor of DR in N0 and N+ hormone receptor–positive patients treated with anastrozole, adding value to estimates with standard clinicopathologic features.
Effect of Age on Outcome of Reduced-Intensity Hematopoietic Cell Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission or With Myelodysplastic Syndrome
Authors: McClune Brian L. , Weisdorf Daniel J. , Pedersen Tanya L. , Tunes da Silva Gisela , Tallman Martin S. , Sierra Jorge , DiPersio John , Keating Armand , Gale Robert P. , George Biju , Gupta Vikas , Hahn Theresa , Isola Luis , Jagasia Madan , Lazarus Hillard , Marks David , Maziarz Richard , Waller Edmund K. , Bredeson Chris , Giralt Sergio
Published: March 2010

Purpose

Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) primarily afflict older individuals. Hematopoietic cell transplantation (HCT) is generally not offered because of concerns of excess morbidity and mortality. Reduced-intensity conditioning (RIC) regimens allow increased use of allogeneic HCT for older patients. To define prognostic factors impacting long-term outcomes of RIC regimens in patients older than age 40 years with AML in first complete remission or MDS and to determine the impact of age, we analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR).

Patients and Methods

We reviewed data reported to the CIBMTR (1995 to 2005) on 1,080 patients undergoing RIC HCT. Outcomes analyzed included neutrophil recovery, incidence of acute or chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, disease-free survival (DFS), and overall survival (OS).

Results

Univariate analyses demonstrated no age group differences in NRM, grade 2 to 4 acute GVHD, chronic GVHD, or relapse. Patients age 40 to 54, 55 to 59, 60 to 64, and ≥ 65 years had 2-year survival rates as follows: 44% (95% CI, 37% to 52%), 50% (95% CI, 41% to 59%), 34% (95% CI, 25% to 43%), and 36% (95% CI, 24% to 49%), respectively, for patients with AML (P = .06); and 42% (95% CI, 35% to 49%), 35% (95% CI, 27% to 43%), 45% (95% CI, 36% to 54%), and 38% (95% CI, 25% to 51%), respectively, for patients with MDS (P = .37). Multivariate analysis revealed no significant impact of age on NRM, relapse, DFS, or OS (all P > .3). Greater HLA disparity adversely affected 2-year NRM, DFS, and OS. Unfavorable cytogenetics adversely impacted relapse, DFS, and OS. Better pre-HCT performance status predicted improved 2-year OS.

Conclusion

With these similar outcomes observed in older patients, we conclude that older age alone should not be considered a contraindication to HCT.