bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness of exercise on prescription with telephone support among women in general practice over 2 years
Authors: Elley C Raina , Garrett Sue , Rose Sally B , O'Dea Des , Lawton Beverley A , Moyes Simon A , Dowell Anthony C
Published: November 2010

Aim

To assess the cost-effectiveness of exercise on prescription with ongoing support in general practice.

Methods

Prospective cost-effectiveness study undertaken as part of the 2-year Women's lifestyle study randomised controlled trial involving 1089 ‘less-active’ women aged 40–74. The ‘enhanced Green Prescription’ intervention included written exercise prescription and brief advice from a primary care nurse, face-to-face follow-up at 6 months, and 9 months of telephone support. The primary outcome was incremental cost of moving one ‘less-active’ person into the ‘active’ category over 24 months. Direct costs of programme delivery were recorded. Other (indirect) costs covered in the analyses included participant costs of exercise, costs of primary and secondary healthcare utilisation, allied health therapies and time off work (lost productivity). Cost–effectiveness ratios were calculated with and without including indirect costs.

Results

Follow-up rates were 93% at 12 months and 89% at 24 months. Significant improvements in physical activity were found at 12 and 24 months (p<0.01). The exercise programme cost was New Zealand dollars (NZ$) 93.68 (€45.90) per participant. There was no significant difference in indirect costs over the course of the trial between the two groups (rate ratios: 0.99 (95% CI 0.81 to 1.2) at 12 months and 1.01 (95% CI 0.83 to 1.23) at 24 months, p=0.9). Cost–effectiveness ratios using programme costs were NZ$687 (€331) per person made ‘active’ and sustained at 12 months and NZ$1407 (€678) per person made ‘active’ and sustained at 24 months.

Conclusions

This nurse-delivered programme with ongoing support is very cost-effective and compares favourably with other primary care and community-based physical activity interventions internationally.
New method to identify athletes at high risk of ACL injury using clinic-based measurements and freeware computer analysis
Authors: Myer Gregory D , Ford Kevin R , Hewett Timothy E
Published: November 2010

Background

High knee abduction moment (KAM) landing mechanics, measured in the biomechanics laboratory, can successfully identify female athletes at increased risk for anterior cruciate ligament (ACL) injury.

Methods

The authors validated a simpler, clinic-based ACL injury prediction algorithm to identify female athletes with high KAM measures. The validated ACL injury prediction algorithm employs the clinically obtainable measures of knee valgus motion, knee flexion range of motion, body mass, tibia length and quadriceps-to-hamstrings ratio. It predicts high KAMs in female athletes with high sensitivity (77%) and specificity (71%).

Conclusion

This report outlines the techniques for this ACL injury prediction algorithm using clinic-based measurements and computer analyses that require only freely available public domain software.
High-density tissue microarrays from prostate needle biopsies
Authors: McCarthy F , Dennis N , Flohr P , Jhavar S , Parker C , Cooper C S
Published: November 2010

Background

Formalin-fixed prostate biopsies are frequently the only tissue collected at the time of prostate cancer diagnosis. There is therefore a requirement for techniques that allow the use of these prostate biopsy specimens in a high-throughput analysis of immunohistochemical and fluorescence-in-situ-hybridisation-detected biomarkers.

Methods

The authors have previously described methods that allow tissue microarray (TMA) construction from prostate biopsies. Here, we describe significant technical innovations that provide an easier and more robust system of biopsy–TMA construction.

Results and discussion

The TMAs produced are of a high density (up to 104 cores each, 8×13) and allow a multiplex analysis of biomarkers in the context of clinical trials.
Retractions in the scientific literature: do authors deliberately commit research fraud?
Authors: Steen R Grant
Published: November 2010

Background

Papers retracted for fraud (data fabrication or data falsification) may represent a deliberate effort to deceive, a motivation fundamentally different from papers retracted for error. It is hypothesised that fraudulent authors target journals with a high impact factor (IF), have other fraudulent publications, diffuse responsibility across many co-authors, delay retracting fraudulent papers and publish from countries with a weak research infrastructure.

Methods

All 788 English language research papers retracted from the PubMed database between 2000 and 2010 were evaluated. Data pertinent to each retracted paper were abstracted from the paper and the reasons for retraction were derived from the retraction notice and dichotomised as fraud or error. Data for each retracted article were entered in an Excel spreadsheet for analysis.

Results

Journal IF was higher for fraudulent papers (p<0.001). Roughly 53% of fraudulent papers were written by a first author who had written other retracted papers (‘repeat offender’), whereas only 18% of erroneous papers were written by a repeat offender (χ=88.40; p<0.0001). Fraudulent papers had more authors (p<0.001) and were retracted more slowly than erroneous papers (p<0.005). Surprisingly, there was significantly more fraud than error among retracted papers from the USA (χ2=8.71; p<0.05) compared with the rest of the world.

Conclusions

This study reports evidence consistent with the ‘deliberate fraud’ hypothesis. The results suggest that papers retracted because of data fabrication or falsification represent a calculated effort to deceive. It is inferred that such behaviour is neither naïve, feckless nor inadvertent.
Experimental exploration of the stratigraphy of fjords fed by glaciofluvial systems
Authors: Overeem Irina , Syvitski James P. M.
Published: November 2010

Whereas most Late Quaternary sedimentary systems experienced only sea-level rise, fjords record unique sequences because rapid uplift after the unloading of the Last Glacial Maximum (LGM) ice sheets outpaced global eustatic sea-level rise. This study aims to disentangle how rapid initial uplift and high variability of eustatic sea-level change affects fjord sedimentary records. Two numerical models are coupled, ICE-5G and SedFlux, and show that timing and duration of deglaciation and total uplift strongly affect fjord stratigraphy. The ICE-5G model predicts a number of distinct time intervals during which many fjords deglaciate, independent of latitude and short-term climate. Deglaciation of the entire fjord system takes significantly longer (
c.
6 ka) for fjords that deglaciate early (17–15 ka BP) than for fjords deglaciating after 9 ka BP (
c.
1 ka). Exponential uplift curves totalled
c.
220–280 m, and have half-lives of 1–1.4 ka.

High uplift rates consistently cause rapid progradation of the rivermouth over tens of kilometres. Thick packages of glaciomarine, and glaciofluvial sediments emerged above sea level and are subsequently incised. Sensitivity tests predict high frequency of submarine mass movements. Fjords that deglaciated early additionally show deposition to be strongly dominated by rapid sea-level rise; signs of drowning are pronounced and subsequent thick fine-grained sequences aggrade. We conclude that recently deglaciated fjords record solely deposition under falling sea-level and thus provide the best modern analogues of forced-regressive systems.
Late Weichselian and Holocene sedimentary environments and glacial activity in Billefjorden, Svalbard
Authors: Baeten Nicole J. , Forwick Matthias , Vogt Christoph , Vorren Tore O.
Published: November 2010

Swath bathymetry data and one sediment core were used to improve the understanding of the Late Weichselian and Holocene glacier activity in Billefjorden, Svalbard. Grounded ice existed in Billefjorden prior to 11.23 cal ka BP (calendar years before present), depositing a basal till and producing glacial lineations. The glacier front retreated from the central parts to the inner parts of the fjord between
c.
11.23 and 11.2 cal ka BP. Annual recessional moraines suggest that this retreat occurred at a rate of up to 170 m a
−1
. During the early Holocene, the glacier Nordenskiöldbreen was comparatively small and sediment supply to central Billefjorden occurred mainly from the fjord sides. An increase in ice rafting around 7930 cal a BP is ascribed to enhanced sea-ice formation. The activity of Nordenskiöldbreen increased around 5470 cal a BP. Ice rafting was generally low during the past
c.
3230 a. This was most likely related to the formation of a more permanent sea-ice cover. Nordenskiöldbreen reached its maximum Holocene extent around AD 1900, generating glacial lineations and depositing a terminal moraine in the inner fjord. Annual recessional moraines were formed during its subsequent retreat. Icebergs from Nordenskiöldbreen generated iceberg ploughmarks during the late Holocene.
Climate proxies for recent fjord sediments in the inner Sognefjord region, western Norway
Authors: Paetzel Matthias , Dale Torbjørn
Published: November 2010

Three high-resolution sediment cores from the periodically anoxic Inner Barsnesfjord and the oxic Outer Barsnesfjord and Sogndalsfjord, Western Norway, are analysed for signals of climate variation. Sedimentation rates are 0.85, 0.75 and 0.45 cm a
−1
, respectively. Sediment slices are taken of 0.3–0.5 cm thickness revealing annual resolution. Corresponding peaks of mineral clay particles, total organic matter and freshwater diatoms correlate well with maxima in regional precipitation, temperature and cloud cover over the last 20 years. This regional climate record is also correlated to the wider NAO (North Atlantic Oscillation) winter index, northern hemisphere temperature and solar activity (cosmic rays and open solar flux) based on 60 years of continuous observation. There is a strong indication that the fjord sediment record contains a climate archive spanning the last 20–100 a; it is suggested that these proxies might also work on longer timescales. A simple box model is presented describing the use of the sediment record for the interpretation of climate variability on a regional scale and at a longer timescale on a millennium scale. It is predicted that this model can be transferred to sediment settings of similar regional climate influence.
Fjord systems and archives: a review
Authors: Howe John A. , Austin William E. N. , Forwick Matthias , Paetzel Matthias , Harland Rex , Cage Alix G.
Published: November 2010

Fjords are glacially over-deepened semi-enclosed marine basins, typically with entrance sills separating their deep waters from the adjacent coastal waters which restrict water circulation and thus oxygen renewal. The location of fjords is principally controlled by the occurrence of ice sheets, either modern or ancestral. Fjords are therefore geomorphological features that represent the transition from the terrestrial to the marine environment and, as such, have the potential to preserve evidence of environmental change. Typically, most fjords have been glaciated a number of times and some high-latitude fjords still possess a resident glacier. In most cases, glacial erosion through successive glacial/interglacial cycles has ensured the removal of sediment sequences within the fjord. Hence the stratigraphic record in fjords largely preserves a glacial-deglacial cycle of deposition over the last 18 ka or so. Sheltered water and high sedimentation rates have the potential to make fjords ideal depositional environments for preserving continuous records of climate and environmental change with high temporal resolution. In addition to acting as high-resolution environmental archives, fjords can also be thought of as mini-ocean sedimentary basin laboratories. Fjords remain an understudied and often neglected sedimentary realm. With predictions of warming climates, changing ocean circulation and rising sea levels, this volume is a timely look at these environmentally sensitive coastlines.

Supplementary material:

The Glossary is available at:
http://www.geolsoc.org.uk/SUP18440
.
Holocene climate variations at the entrance to a warm Arctic fjord: evidence from Kongsfjorden trough, Svalbard
Authors: Skirbekk Kari , Kristensen Dorthe Klitgaard , Rasmussen Tine L. , Koç Nalan , Forwick Matthias
Published: November 2010

The North Atlantic Current transports warm and salty water into the Nordic Seas and continues northwards into the Arctic Ocean as the West Spitsbergen Current. This current flows along the west coast of the Svalbard archipelago and into the fjords and troughs on the Svalbard shelf. We have investigated a core (NP05-11-21GC) from the Kongsfjorden trough, which spans the last 12 ka. The core site presently experiences seasonal inflow of Atlantic Water masses, and may therefore provide a record of past variations in Atlantic Water inflow to the Arctic. Lithological analysis and benthic foraminifera have been used to reconstruct the palaeoceanographic development in the area. The results show that cold and harsh conditions prevailed during the late part of the Younger Dryas and that the site was in proximity to glaciers. After 11.8 ka BP the first influence of Atlantic Water is seen in the fauna. This was followed by changes in glacial activity at 11.5 ka BP. During the period 11.5–10.6 ka BP the fauna indicate increased influence of Atlantic Water and the final deglaciation of the fjord after the Younger Dryas period. These initial ameliorated conditions were interrupted by a 250-year long cooling starting at 11.3 ka BP, corresponding to the Preboreal Oscillation. After 10.6 ka BP a marked change from an ice proximal to ice distal environment occurred accompanied by the strong influence of Atlantic Water masses. In the Mid-Holocene at 7 ka BP, the influence of Atlantic Water diminished but no sign of an immediate response of the glaciers to this are found in the core. The evidence suggests that intensification of glacial activity started as late as
c
. 3.5 ka BP. Comparing the core from Kongsfjorden trough with two shelf records from Svalbard generally shows similar faunal development although some differences exist. These are assumed to be related to the distance of each record to the position of the Arctic front.
Using seismic facies and pollen analyses to evaluate climatically driven change in a Scottish sea loch (fjord) over the last 20 ka
Authors: Baltzer Agnès , Bates Richard , Mokeddem Zohra , Clet-Pellerin Martine , Walter-Simonnet Anne-Véronique , Bonnot-Courtois Chantal , Austin William E. N.
Published: November 2010

Loch Sunart is a glacially over-deepened sea loch (fjord) on the west coast of Scotland, UK. The loch is divided into three sub-basins, separated by relatively shallow and narrow sills. A programme of data collection including high-resolution bathymetric sonar and sub-bottom seismic surveys were conducted in the loch as part of an investigation into the sedimentological and climatic change signatures preserved in western sea lochs since the Last Glacial Maximum. Very-high-resolution sub-bottom profiles were obtained using the SEISTEC boomer system. The seismic profiles revealed an igneous and metamorphic basement covered by a 10–70 m thick sediment sequence. Five different acoustic facies were recognized and interpreted in terms of glacial activity, ice retreat and subsequent Holocene sedimentation. These facies have been correlated to sediments sampled in a radiocarbon-dated 12 m long giant piston core (MD04-2833) acquired from the main basin of Loch Sunart. Pollen analyses conducted along the length of the core, together with
14
C dating, indicate a complex series of palaeoclimate changes in the loch. In particular, five distinct cooling events have been recognized
c
. 9.8, 8.2, 5.8, 1.2 cal ka BP and 771–1211 cal a BP (possibly the Little Ice Age), corresponding to phases of Holocene rapid climate change.
Short-term hydrographic variability in a stratified Arctic fjord
Authors: Skarðhamar J. , Svendsen H.
Published: November 2010

Fjords in the Arctic often have a more complex circulation pattern than the classical two-dimensional estuarine circulation. This is due to the effects of the Earth's rotation on stratified waters in wide fjords. Observations from a semi-enclosed fjord basin, Van Mijenfjorden on Spitsbergen, show that the hydrography and circulation vary considerably on short timescales (hours) in the summer season. The depth and distribution of the low salinity upper water layer respond quickly to changes in the wind field. The Coriolis effect has an essential impact on the circulation, inducing eddy-like flow patterns and strong cross-fjord gradients. Within the upper layer, the lowest salinity values and highest temperatures were found on the northern side of the fjord in calm wind periods. When the wind was strong from the west, the cross-fjord gradients were reversed. Internal wave activity contributes to large vertical displacement of water below the upper layer. Knowledge of such strongly variable hydrographic conditions in fjords are important for sampling strategy and interpretation of data, for instance of primary production and sedimentation processes, and for the understanding of fjords as depositional systems.
Dinoflagellate cysts as proxies for palaeoceanographic conditions in Arctic fjords
Authors: Howe John A. , Harland Rex , Cottier Finlo R. , Brand Tim , Willis Kate J. , Berge Jørgen R. , Grøsfjeld Kari , Eriksson Anita
Published: November 2010

The potential of using dinoflagellate cysts as proxies for palaeoceanographic conditions and as monitors of the dynamic marine environment of climatically sensitive Arctic fjords was investigated with sediment traps. Dinoflagellate cysts were analysed from three separate deployments in two high Arctic fjords in the Svalbard archipelago. Two deployments in Kongsfjorden on the west coast of Svalbard occurred during 2002 and 2006–2007 and a deployment in Rijpfjorden on the NE coast occurred during 2006–2007. The cyst production displayed peaks of abundance in the spring and late summer with distinct differences in cyst occurrence in different fjords and in different years. The recorded and identified cyst species were consistent both with the hydrography of the fjords and with changes in cyst composition that are comparable to the seasonal shifts in water mass characteristics. The presence of the heterotrophic species
Protoperidinium conicum
in Kongsfjorden during 2002 is of note and may reflect the availability of a particular food source possibly associated with the strong influx of Atlantic Water. Cysts recovered from Kongsfjorden during 2006–2007 were dominated by
Islandinium minutum
, an indicator of cold, polar to subpolar conditions. The temperature and salinity characteristics of the ambient hydrography in this period indicated less influence by Atlantic Water than in 2002, and the cyst production was consistent with regional cyst distribution patterns. In Rijpfjorden, cyst assemblages were dominated by
Pentapharsodinium dalei
, consistent with the fjord being dominated by full Arctic conditions during the mooring deployment and the possible occurrence of stratified water with high productivity during the spring phytoplankton bloom.
High benthic foraminiferal species counts in a Clyde Sea maerl bed, western Scotland
Authors: Austin William E. N. , Cage Alix G.
Published: November 2010

A preliminary investigation of the occurrence of hard-shelled benthic foraminifera in a sample of maerl (gravels derived from calcareous red seaweed) collected from a water depth of 10 m by SCUBA diving in the Clyde Sea, Scotland reveals an exceptionally well-preserved and diverse assemblage. A total of 90 different species were identified, comprising 12 agglutinated, 15 porcelaneous and 63 hyaline types; this represents the highest recorded species count described from the west of Scotland. The assemblage probably represents an integrated record of material derived directly from the maerl (mostly epifaunal types) and material derived from the reworking of adjacent sediments (mostly infaunal types). Maerl deposits represent an important near-shore habitat which appear to have been largely overlooked in regional studies of benthic foraminiferal distribution/ecology.
The importance of PGC-1α in contractile activity-induced mitochondrial adaptations
Authors: Uguccioni Giulia , Hood David A.
Published: November 2010

The transcriptional coactivator PPARγ coactivator-1α (PGC-1α) is a critical regulator of mitochondrial content and function in skeletal muscle. PGC-1α may also mediate mitochondrial adaptations in response to chronic contractile activity (CCA). To characterize the essential role of PGC-1α in organelle biogenesis, C2C12murine myotubes were transfected with PGC-1α-specific siRNA and subjected to electrical stimulation-evoked CCA. CCA enhanced cytochrome c oxidase (COX) activity along with increases in several nuclear-encoded mitochondrial proteins. Transfection of PGC-1α siRNA decreased protein and mRNA of the coactivator by 60%, resulting in decrements of Tfam and COX-IV proteins. The mRNA expression of the PGC-1 family members PGC-1β and PRC, as well as transcription factors NRF-1/2 and ERRα, did not exhibit compensatory changes in response to PGC-1α depletion. However, phosphorylation of AMPK was enhanced in myotubes with reduced levels of PGC-1α. This suggests the presence of metabolic compensatory stress signals in cells deficient in PGC-1α. Our findings reveal that the CCA-induced increases in COX-IV protein and overall mitochondrial content, using both COX activity and organelle fluorescence, are dependent on PGC-1α. However, this was not the case for all proteins, since decreased levels of the coactivator did not attenuate the increases in Tfam and cytochrome c in response to CCA. These data indicate that PGC-1α is necessary for most of the mitochondrial adaptations that occur with CCA but that there are additional pathways that function in parallel with PGC-1α to mediate the elevated expression of specific nuclear-encoded proteins that are vital for mitochondrial function and cell viability.
Analytical construct of reversible desensitization of pituitary-testicular signaling: illustrative application in aging
Authors: Keenan Daniel M. , Iranmanesh Ali , Veldhuis Johannes D.
Published: November 2010

Luteinizing hormone (LH) administered in pharmacological amounts downregulates Leydig cell steroidogenesis. Whether reversible downregulation of physiological gonadotropin drive operates in vivo is unknown. Most of the analytical models of dose-response functions that have been constructed are biased by the assumption that no downregulation exists. The present study employs a new analytical platform to quantify potential (but not required) pulsatile cycles of LH-testosterone (T) dose-response stimulation, desensitization, and recovery (pulse-by-pulse hysteresis) in 26 healthy men sampled every 10 min for 24 h. A sensitivity-downregulation hysteresis construct predicted marked hysteresis with a median time delay to LH dose-response inflection within individual T pulses of 23 min and with median T pulse onset and recovery LH sensitivities of 1.1 and 0.10 slope unit, respectively ( P < 0.001). A potency-downregulation model yielded median estimates of one-half maximally stimulatory LH concentrations (EC50 values) of 0.66 and 7.5 IU/l for onset and recovery, respectively ( P < 0.001). An efficacy-downregulation formulation of hysteresis forecasts median LH efficacies of 20 and 8.3 ng·dl−1·min−1 for onset and offset of T secretory burst, respectively ( P = 0.002). Segmentation of the LH-T data by age suggested greater sensitivity, higher EC50 (increased LH potency), and markedly (2.7-fold) attenuated LH efficacy in older individuals. Each of the three hysteresis models yielded a marked ( P < 0.005) reduction in estimated model residual error compared with no hysteresis. In summary, model-based analyses allowing for (but not requiring) reversible pituitary-gonadal effector-response downregulation are consistent with a hypothesis of recurrent, brief cycles of LH-dependent stimulation, desensitization, and recovery of pulsatile T secretion in vivo and an age-associated reduction of LH efficacy. Prospective studies would be required to prove this aging effect.
Combined mRNA and microRNA profiling reveals that miR-148a and miR-20b control human mesenchymal stem cell phenotype via EPAS1
Authors: Giraud-Triboult Karine , Rochon-Beaucourt Christelle , Nissan Xavier , Champon Benoite , Aubert Sophie , Piétu Geneviève
Published: November 2010

Mesenchymal stem cells (MSCs) are present in a wide variety of tissues during development of the human embryo starting as early as the first trimester. Gene expression profiling of these cells has focused primarily on the molecular signs characterizing their potential heterogeneity and their differentiation potential. In contrast, molecular mechanisms participating in the emergence of MSC identity in embryo are still poorly understood. In this study, human embryonic stem cells (hESs) were differentiated toward MSCs (ES-MSCs) to compare the genetic patterns between pluripotent hESs and multipotent MSCs by a large genomewide expression profiling of mRNAs and microRNAs (miRNAs). After whole genome differential transcriptomic analysis, a stringent protocol was used to search for genes differentially expressed between hESs and ES-MSCs, followed by several validation steps to identify the genes most specifically linked to the MSC phenotype. A network was obtained that encompassed 74 genes in 13 interconnected transcriptional systems that are likely to contribute to MSC identity. Pairs of negatively correlated miRNAs and mRNAs, which suggest miRNA-target relationships, were then extracted and validation was sought with the use of Pre-miRs. We report here that underexpression of miR-148a and miR-20b in ES-MSCs, compared with ESs, allows an increase in expression of the EPAS1 (Endothelial PAS domain 1) transcription factor that results in the expression of markers of the MSC phenotype specification.
Atlas of gene expression in the mouse kidney: new features of glomerular parietal cells
Authors: Cheval Lydie , Pierrat Fabien , Dossat Carole , Genete Mathieu , Imbert-Teboul Martine , Duong Van Huyen Jean-Paul , Poulain Julie , Wincker Patrick , Weissenbach Jean , Piquemal David , Doucet Alain
Published: November 2010

To gain molecular insight into kidney function, we performed a high-resolution quantitative analysis of gene expression in glomeruli and nine different nephron segments dissected from mouse kidney using Serial Analysis of Gene Expression (SAGE). We also developed dedicated bioinformatics tools and databases to annotate mRNA tags as transcripts. Over 800,000 mRNA SAGE tags were sequenced corresponding to >20,000 different mRNA tags present at least twice in at least one library. Hierarchical clustering analysis of tags demonstrated similarities between the three anatomical subsegments of the proximal tubule, between the cortical and medullary segments of the thick ascending limb of Henle's loop, and between the three segments constituting the aldosterone-sensitive distal nephron segments, whereas the glomerulus and distal convoluted tubule clusterized independently. We also identified highly specific mRNA markers of each subgroup of nephron segments and of most nephron segments. Tag annotation also identified numbers of putative antisense mRNAs. This database constitutes a reference resource in which the quantitative expression of a given gene can be compared with that of other genes in the same nephron segment, or between different segments of the nephron. To illustrate possible applications of this database, we performed a deeper analysis of the glomerulus transcriptome that unexpectedly revealed expression of several ion and water carriers; within the glomerulus, they were found to be preferentially expressed in the parietal sheet. It also revealed the major role of the zinc finger transcription factor Wt1 in the specificity of gene expression in the glomerulus. Finally, functional annotation of glomerulus-specific transcripts suggested a high proliferation activity of glomerular cells. Immunolabeling for PCNA confirmed a high percentage of proliferating cells in the glomerulus parietal sheet.
Pazopanib Reveals a Role for Tumor Cell B-Raf in the Prevention of HER2+ Breast Cancer Brain Metastasis
Authors: Gril Brunilde , Palmieri Diane , Qian Yong , Smart DeeDee , Ileva Lilia , Liewehr David J. , Steinberg Seth M. , Steeg Patricia S.
Published: November 2010

Purpose: Brain metastases of breast cancer contribute significantly to patient morbidity and mortality. We have tested pazopanib, a recently approved antiangiogenic drug that targets VEGFR1, VEGFR2, VEGFR3, PDGFRβ, PDGFRα, and c-kit, for prevention of experimental brain metastases and mechanism of action.

Experimental Design: In vitro assays included B-Raf enzymatic assays, Western blots, and angiogenesis assays. For in vivo assays, HER2 transfectants of the brain seeking sublines of MDA-MB-231 cells (231-BR-HER2) and MCF7 cells (MCF7-HER2-BR3, derived herein) were injected into the left cardiac ventricle of mice and treated with vehicle or pazopanib beginning on day 3 postinjection. Brain metastases were counted histologically, imaged, and immunostained.

Results: Treatment with 100 mg/kg of pazopanib resulted in a 73% decline in large 231-BR-HER2 metastases (P < 0.0001) and a 39% decline in micrometastases (P = 0.004). In vitro, pazopanib was directly antiproliferative to 231-BR-HER2 breast cancer cells and inhibited MEK and ERK activation in vitro despite B-Raf and Ras mutations. Enzymatic assays demonstrated that pazopanib directly inhibited the wild type and exon 11 oncogenic mutant, but not the V600E mutant forms of B-Raf. Activation of the B-Raf targets pERK1/2 and pMEK1/2 was decreased in pazopanib-treated brain metastases whereas blood vessel density was unaltered. In the MCF7-HER2-BR3 experimental brain metastasis model, pazopanib reduced overall brain metastasis volume upon magnetic resonance imaging (MRI) by 55% (P = 0.067), without affecting brain metastasis vascular density.

Conclusions: The data identify a new activity for pazopanib directly on tumor cells as a pan-Raf inhibitor and suggest its potential for prevention of brain metastatic colonization of HER2+ breast cancer. Clin Cancer Res; 17(1); 142–53. ©2010 AACR.
Compassionate Use of Linezolid for Adult Taiwanese Patients with Bone and Joint Infections
Authors: Lu Po-Liang , Wang Jann-Tay , Chen Chih-Jung , Chen Wan-Chin , Chen Tun-Chieh , Hwang Yhu-Chering , Chang Shan-Chwen
Published: November 2010

Background: Compassionate use of linezolid for bone and joint infections has been reported and hematological adverse reactions are a cause for concern. A similar experience in Asian people has not been reported. Methods: Adult cases that received linezolid for bone and joint infections at 3 Taiwanese medical centers from 2002 to 2006 were analyzed. We investigated factors associated with treatment outcome and hematological adverse reactions. Results: Of the 51 cases that received linezolid for more than 3 days, 41 (80.4%) had a favorable outcome and 10 had a failed outcome. Based on univariate analysis, patients with renal/urinary tract diseases, gastrointestinal diseases, higher WBC counts, a higher alanine aminotransferase level, or a higher creatinine level prior to linezolid treatment were significantly associated with a failed outcome. Based on multivariate analysis, underlying gastrointestinal disease was the only significant factor for a failed outcome. Six patients stopped linezolid use due to adverse reactions. A failed outcome was significantly associated with anemia caused by linezolid. Conclusion: Linezolid is an effective salvage agent for bone and joint infections. However, adverse effects, especially hematological reactions, may cause drug discontinuation.
The Immunomodulatory Effect of the Antidepressant Sertraline in an Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis
Authors: Taler Michal , Gil-Ad Irit , Korob Inna , Weizman Abraham
Published: November 2010

Background: We have previously demonstrated the immunomodulatory activity of some selective serotonin reuptake inhibitors. Objectives: In this research, we performed an in vivo/ex vivo study to evaluate the potential immunosuppressive effect of sertraline in an experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Methods: Mice (C57/bl EAE) were treated with sertraline (5 mg/kg) or dexamethasone (1 mg/kg) 7 days after EAE induction and then 3 times weekly (for 3 weeks). Results: Sertraline modestly improved the clinical score of EAE and attenuated the disease-induced weight loss. Sertraline also significantly decreased ex-vivo splenocyte viability, proliferation and secretion of pro-inflammatory cytokines in EAE mice. Conclusions: We suggest that sertraline might be an add-on option for multiple sclerosis treatment.
A Systematic Review of the Incidence and Prevalence of Long-Term Neurological Conditions in the UK
Authors: Hoppitt Thomas , Pall Hardev , Calvert Mel , Gill Paramjit , Yao Guiqing , Ramsay Jill , James Gill , Conduit Jacky , Sackley Cath
Published: November 2010

Background: Updated, robust estimates of the incidence and prevalence of rare long-term neurological conditions in the UK are not available. Global estimates may be misrepresentative as disease aetiology may vary by location. Objectives: To systematically review the incidence and prevalence of long-term neurological conditions in the UK since 1988. Search Strategy: Medline (January 1988 to January 2009), Embase (January 1988 to January 2009), CINAHL (January 1988 to January 2009) and Cochrane CENTRAL databases. Selection Criteria: UK population-based incidence/prevalence studies of long-term neurological conditions since 1988. Exclusion criteria included inappropriate diagnoses and incomprehensive case ascertainment. Data Collection and Analysis: Articles were included based on the selection criteria. Data were extracted from articles with ranges of incidence and prevalence reported. Main Results: Eight studies met the criteria (3 on motor neurone disease; 4 on Huntington’s disease; 1 on progressive supranuclear palsy). The incidence of motor neurone disease ranged from 1.06 to 2.4/100,000 person-years. The prevalence ranged from 4.02 to 4.91/100,000. The prevalence of Huntington’s disease ranged from 4.0 to 9.94/100,000. The prevalence of progressive supranuclear palsy ranged from 3.1 to 6.5/100,000. Conclusions: The review updates the incidence/prevalence of long-term neurological conditions. Future epidemiological studies must incorporate comprehensive case ascertainment methods and strict diagnostic criteria.
Image Eaters: Big Art Group Brings the Noise
Authors: Gallagher-Ross Jacob
Published: November 2010

Making noisy art for noisy times, New York ensemble Big Art Group's hyper-mediated aesthetic stages the sensory surfeit of modern life. Employing batteries of screens, prismatic live-feed video, and roaring digital soundscapes, the company's experiments with attention and perception create a new model for political theatre grounded in the contested dynamics of spectatorship.
Association Between Muscle Mass, Leg Strength, and Fat Mass With Physical Function in Older Adults: Influence of Age and Sex
Authors: Bouchard Danielle R. , Héroux Mariane , Janssen Ian
Published: November 2010

Objective: The purposes of this study were to determine the relationship between muscle mass, muscle strength, muscle quality, and fat mass with a composite measure of physical function in older adults, and to determine whether these relations differed by age and sex. Method: Participants consisted of 1280 adults aged ≥ 55 yr from the NHANES study. Reduced rank regression was used to identify patterns of muscle mass, muscle strength, muscle quality, and fat mass related to physical function. Results: A single relevant pattern emerged that included leg strength and fat mass as predictors of the 7 physical function variables. The leg strength loading was significantly greater than the fat mass loading in men and women aged 55-64 and ≥75, and differed between sexes. Conclusion: Leg strength and fat mass best predict physical function in older adults and the relative importance varies according to age and sex.
Understanding Women’s Work through the Confluence of Gender, Race, and Social Class
Authors: Hofman Nila Ginger
Published: November 2010

This article examines the experiences of women’s work by focusing on the lives of working class and middle class women, African Americans, Caucasians and Latinas. Research for this project was conducted in the Humboldt Park neighborhood of Chicago, Illinois, with adult women who live, go to school, or work there. We spoke with adult women working toward their General Education Degree and those with higher levels of education. Using intersectional analysis and a cultural constructivist framework, this study compares these women’s different perceptions of the Humboldt Park neighborhood and their varying experiences as participants in the labor market and unpaid household labor.
‘Family Structure’: Intractable Eurocentric Fantasies in Contemporary Israel
Authors: Yonah Yossi , Ram Haggai , Markovich Dalya
Published: November 2010

This article offers a critical study of the iteration and reiteration of Israel’s national identity. Thus this study falls within a well charted research terrain. And like many studies falling within its purview, it is also intended to do more than just describe attempts to impose uniform collective identity on obdurate social and cultural diversity. It is intended to examine the national project as ‘a form of cultural elaboration’ entrapped within an insoluble predicament.While aiming at molding a homogeneous national collective out of social and cultural diversity, this project generates intricate dialectics involving practices of social inclusion and exclusion. These dialectics take on board often racial myths. We examine these dialectics and the racial myths associated with them vis-à-vis the iteration and reiteration of Israel’s national identity. Aside from inculcating the belief among Israeli Jews that their identity is reflective of a common cultural heritage that reaches back to times immemorial, these myths also register a yearning to reconnect Israel with its lost European, ‘Judeo-Christian’ heritage. Conveying these aspirations, either covertly or overtly, these myths support and reconfirm existing social and racial hierarchies in Israeli society.
Peshgi Without Bondage: Reconsidering the Links between Debt and Bonded Labour
Authors: Khan Ali
Published: November 2010

This article looks at the link between debt bondage and the ubiquitous advance (or what is called peshgi in Pakistan) in the context of the football-stitching and bangle-making industries of Sialkot and Hyderabad in Pakistan. By drawing on an analysis of the football-stitching and bangle-making industries it disputes the notion that the presence of peshgi inevitably leads to a relationship of debt bondage between employer and workers. This article shows that a sense of shared origin amongst workers and employers can mitigate the factors that lead to a relationship of debt bondage. Specifically, patrilineage ( biraderi ) ties in the case of the bangle-making industry of Hyderabad and common geographical and class origin in the case of the football industry of Sialkot have helped cement ties between workers and employers and led to the prevalence of peshgi without the resulting debt bondage. In the case of both these industries, their unique historical development—with the historical emergence of industrialists in Sialkot from the ranks of the artisans and workers and the migration to Hyderabad after Partition of those belonging to the Ferozabad Siddiqui kinship group—helps explain the absence of a more antagonistic relationship between employers and workers in these industries. This article concludes that peshgi does not always lead to debt bondage and certain factors such as a sense of shared origin or patrilineage ties between workers and employers can explain the existence of peshgi without debt bondage.
“Institutional Work” for What? Problems and Prospects of Institutional Theory
Authors: Willmott Hugh
Published: November 2010

The problems and prospects currently facing Institutional Theory are addressed by scrutinizing recent proposals for focusing upon ‘institutional work’ in a way of that promises to overcome some limitations of its “old,” “neo,” and “entrepreneurialist” incarnations. Current proposals to pay closer attention to ‘institutional work’ are seen to reproduce the dualism of individual (agency) /institution (structure) as they invite a further flip-flop between these poles, To escape this cycle, a start can be made by incorporating into Institutional Theory a critically reflexive appreciation of the ‘individual’ as an institution. Such a move is consistent with a contemporary interest in bridging institutional and critical scholarly traditions. In constructing this bridge, the challenge is to advance scholarship in a direction that, being collaborative rather than predatory, does not obfuscate or domesticate the emancipatory intent of critical analysis.
COPD, chronic bronchitis and capacity for day-to-day activities: Negative impact of illness on the health-related quality of life
Authors: Kanervisto Merja , Saarelainen Seppo , Vasankari Tuula , Jousilahti Pekka , Heistaro Sami , Heliövaara Markku , Luukkaala Tiina , Paavilainen Eija
Published: November 2010

The aim of this study was to investigate the negative impact of illness on health-related quality of life (HRQoL) of people with chronic obstructive pulmonary disease (COPD) or chronic bronchitis. The study population consisted of the participants (N = 8028) of a health examination survey conducted in Finland. The sample in the present substudy was composed of 4718 participants who had complete information about spirometry. Variables age, gender, body mass index (BMI), illnesses, smoking in lifetime, education, FEV1% and incomes were entered in blockwise bivariate regression analysis to examine the relationships between capability for day-to-day activities (physical, psychological and social functioning) of those with COPD. Also, COPD (n = 277) and chronic bronchitis (n = 630) were compared with the general population (n = 3817). Study results showed that women with COPD had worse HRQoL than men, regarding the activities in daily living (ADL; odds ratio [OR] 2.63, 95% confidence interval [Cl] 1.15—5.99), instrumental activities of daily living (IADL; OR 4.23, 95% Cl 1.92—9.29) and exercise (OR 2.66, 95% Cl 1.21—5.84). Compared with the general population, people with chronic bronchitis were associated with poor ADL, IADL and exercise, (OR 1.58, 95% Cl 1.32— 1.92). Those with COPD, had difficulties managing in ADL (OR 4.02, 95% Cl 2.98—5.44), IADL (OR 3.27, 95% Cl 2.43—4.39), exercise (OR 3.35, 95% Cl 2.47 to 4.53). In this representative population-based sample, COPD and chronic bronchitis mean a significantly poor capability in physical functioning. People with chronic bronchitis experienced their daily life to be worse compared with the general population. Reductions in physical functioning for women and especially with COPD were also noteworthy.
Review Series: What goes around, comes around: childhood influences on later lung health?: Long-term follow-up of infants with lung disease of prematurity
Authors: Narang Indra
Published: November 2010

The incidence of live preterm birth is increasing and concomitantly the survival of preterm babies has increased over the last 30 years due to advances in neonatal care. Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease that develops as a consequence of perinatal and/or neonatal lung injury following preterm birth and the pathology has also changed with changes in neonatal care. There are data suggesting that there is increased respiratory morbidity of ex-preterm subjects in childhood. It is only now that large populations of preterm subjects are reaching adulthood and may be at risk of persistent respiratory morbidity. This review will summarize the current knowledge in adulthood of respiratory sequelae following preterm birth; specifically it will review respiratory symptoms, pulmonary function, exercise capacity and structural lung disease as determined by high resolution computed tomography scans in ex-preterm survivors with and without BPD. Whether prematurity-related lung disease is associated with chronic obstructive airways disease will be discussed.
The endurance shuttle walk test: An alternative to the six-minute walk test for the assessment of ambulatory oxygen
Authors: Revill SM , Noor MZ , Butcher G. , Ward MJ
Published: November 2010

UK guidelines for domiciliary oxygen have suggested the six-minute walk test or shuttle walk tests as suitable functional measures for the clinical assessment of ambulatory oxygen (AO). To date, there is limited evidence that would support the use of shuttle walk tests as assessment tools for AO. The endurance shuttle walk test (ESWT) is used increasingly as an assessment tool within pulmonary rehabilitation (PR) but its potential as an investigative test for AO has not been explored. Using the same test for both PR and AO assessment is appealing since it would improve efficiency and act to standardise outcome measures in this patient population. The aim of this study was to examine the responsiveness and repeatability of the ESWT to AO and to compare the response with that of the six-minute walk test (6MWT). Twenty-three patients with chronic obstructive pulmonary disease (COPD) performed, in random order, the ESWT and the 6MWT on air and whilst breathing AO. Oxygen saturation and Borg ratings of breathlessness and perceived exertion were recorded. On a third day, eleven patients repeated the ESWT with AO in order to measure repeatability. There was a significantly greater change in the ESWT with oxygen than the change recorded from the 6MWT (66 [91] vs 6 [28] m respectively; P < .05). When repeated on a separate day, the mean difference (95% CI) between distances walked on the ESWT with AO was 0.91 (-47, 49) m. The ESWT was more responsive than the 6MWT for detecting improvements in walking endurance whilst breathing AO.
Data collectors’ field journals as tools for research
Authors: Friedemann Marie-Luise , Mayorga Carlos , Jimenez Luz Dary
Published: November 2010

With rising numbers of families giving care to elderly loved ones, novel methods and sources of data need to be used to obtain comprehensive information about family caregiving patterns. The purpose of this paper is to present the interviewers’ reflective journals as a source of rich data. Data collectors interviewed Hispanic family caregivers as part of a quantitative study of caregiving patterns. The stories derived from the personal journals brought to life three themes: caregiving as responsibility; creativity in giving care; and resistance to delegating tasks. Well-written journals have the potential of enhancing the interpretation of data collected by other means and of raising the quality of interviews and data through introspection and cultural understanding of the caregiving reality.