bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying the RR of harm to self and others from substance misuse: results from a survey of clinical experts across Scotland
Authors: Taylor Mark , Mackay Kirsty , Murphy Jen , McIntosh Andrew , McIntosh Claire , Anderson Seonaid , Welch Killian 
Published: July 2012

ObjectiveTo produce an expert consensus hierarchy of harm to self and others from legal and illegal substance use.DesignStructured questionnaire with nine scored categories of harm for 19 different commonly used substances.Setting/participants292 clinical experts from across Scotland.ResultsThere was no stepped categorical distinction in harm between the different legal and illegal substances. Heroin was viewed as the most harmful, and cannabis the least harmful of the substances studied. Alcohol was ranked as the fourth most harmful substance, with alcohol, nicotine and volatile solvents being viewed as more harmful than some class A drugs.ConclusionsThe harm rankings of 19 commonly used substances did not match the A, B, C classification under the Misuse of Drugs Act. The legality of a substance of misuse is not correlated with its perceived harm. These results could inform any legal review of drug misuse and help shape public health policy and practice.
Physiotherapy rehabilitation following lumbar spinal fusion: a systematic review and meta-analysis of randomised controlled trials
Authors: Rushton Alison , Eveleigh Gillian , Petherick Emma-Jane , Heneghan Nicola , Bennett Rosalie , James Gill , Wright Chris 
Published: July 2012

ObjectiveTo evaluate the effectiveness of physiotherapy intervention following lumbar spinal fusion.DesignSystematic review and meta-analysis. 2 independent reviewers searched information sources, assessed studies for inclusion and evaluated risk of bias. Quantitative synthesis using standardised mean differences was conducted on comparable outcomes across trials with similar interventions.Information sourcesPredefined terms were employed to search electronic databases. Additional studies were identified from key journals, reference lists, authors and experts.Eligibility criteria for included studiesRandomised control trials published in English prior to 30 September 2011 investigating physiotherapy outpatient management of patients (>16 years), following lumbar spinal fusion, with measurements reported on one or more outcome of disability, function and health were included.Results2 Randomised control trials (188 participants) from two countries were included. Both trials included a behavioural and an exercise intervention. 1 trial was evaluated as high risk of bias and one as unclear. 159 participants were incorporated in the meta-analysis. Although evidence from both trials suggested that intervention might reduce back pain short term (6 months) and long term (12 months and 2 years), and a behavioural intervention might be more beneficial than an exercise intervention, the pooled effects (0.72, 95% CI −0.25 to 1.69 at 6 months; 0.52, 95% CI −0.45 to 1.49 at 12 months and 0.75, 95% CI −0.46 to 1.96 at 2 years) did not demonstrate statistically significant effects. There was no evidence that intervention changes pain in the short (6 months) or long term (12 months and 2 years). The wide CI for pooled effects indicated that intervention could be potentially beneficial or harmful. Considerable heterogeneity was evident.ConclusionsInconclusive, very low-quality evidence exists for the effectiveness of physiotherapy management following lumbar spinal fusion. Best practice remains unclear. Limited comparability of outcomes and retrieval of only two trials reflect a lack of research in this area that requires urgent consideration.
Stress-dependent behavior of saturated clay
Authors: Abdulhadi Naeem O. , Germaine John T. , Whittle Andrew J. 
Published: July 2012

A program of K0-consolidated undrained triaxial compression tests has been performed to investigate the effects of consolidation stress level on the compression and shear behavior of resedimented Boston blue clay (RBBC). Specimens were consolidated to maximum vertical effective stresses in the range 0.15–10 MPa and tested at three overconsolidation ratios (OCR): 1, 2, and 4. The results show that the virgin compression curves are essentially linear in e–log[Formula: see text] space over the consolidation stress range. However, the normally consolidated K0stress ratio increases with the level of consolidation stress. The stress–strain–strength properties measured in undrained shear are significantly affected by the consolidation stress level at each OCR and show indications of non-normalizable behavior. At high pressures, the undrained shear stress–strain behavior becomes more ductile, requiring larger strains to mobilize peak resistance and exhibiting less post-peak strain-softening. The undrained strength ratio (su/[Formula: see text]) is not uniquely controlled by OCR as suggested by the SHANSEP equation, but consistently decreases with increasing consolidation effective stress. There is notable reduction in the stiffness ratio (Eu/[Formula: see text]) with stress level, and significant decrease in the large-strain friction angle.
Longitudinal Change in Telomere Length and the Chronic Stress Response in a Randomized Pilot Biobehavioral Clinical Study: Implications for Cancer Prevention
Authors: Biegler Kelly A. , Anderson Amanda K. L. , Wenzel Lari B. , Osann Kathryn , Nelson Edward L. 
Published: July 2012

Abstract
Shortened telomere length is associated with increased cancer incidence and mortality. Populations experiencing chronic stress have accelerated telomere shortening. In this exploratory study, we examined associations between longitudinal changes in patient reported outcomes (PRO) of psychologic distress and peripheral blood mononuclear cell (PBMC) telomere length to test the hypothesis that modulation of the chronic stress response would also modulate telomere dynamics. Archived PBMC specimens (N = 22) were analyzed from a completed and reported randomized, longitudinal trial that showed a psychosocial telephone counseling intervention improved quality of life (QOL) and modulated stress-associated biomarkers in cervical cancer survivors. PROs and biospecimens were collected at baseline and 4 months postenrollment. Telomere length of archived PBMCs was evaluated using the flow-FISH assay. Longitudinal changes in psychologic distress, measured by the Brief Symptom Inventory-18, were significantly associated with increased telomere length within the CD14+ (monocyte) population (r = −0.46, P = 0.043); a similar trend was observed for the CD14− population. Longitudinal changes in telomere length of the CD14− subset, primarily T lymphocytes, were associated with longitudinal increases in the naive T-cell population (r = 0.49, P = 0.052). Alterations in the chronic stress response were associated with modulation of telomere length in PBMCs, with evidence for mobilization of “younger” cells from progenitor populations. These data provide preliminary support for the (i) capacity to modulate the chronic stress response and the associated accelerated telomere shortening, (ii) inclusion of telomere length in the biobehavioral paradigm, and (iii) potential link between the chronic stress response and biologic mechanisms responsible for genomic integrity and carcinogenesis. Cancer Prev Res; 5(10); 1173–82. ©2012 AACR.
An EMILIN1-Negative Microenvironment Promotes Tumor Cell Proliferation and Lymph Node Invasion
Authors: Danussi Carla , Petrucco Alessandra , Wassermann Bruna , Modica Teresa Maria Elisa , Pivetta Eliana , Belluz Lisa Del Bel , Colombatti Alfonso , Spessotto Paola 
Published: July 2012

Abstract
The evidence that EMILIN1 (Elastic Microfibril Interface Located proteIN) deficiency in Emilin1−/− mice caused dermal and epidermal hyperproliferation and an abnormal lymphatic phenotype prompted us to hypothesize the involvement of this extracellular matrix component in tumor development and in lymphatic metastasis. Using the 12-dimethylbenz(α)anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA) two-stage model of skin carcinogenesis, we found that Emilin1−/− mice presented an accelerated formation, a higher incidence, and the development of a larger number of tumors compared with their wild-type littermates. EMILIN1-negative tumors showed more Ki67-positive proliferating cells and higher levels of pErk1/2. In these tumors, PTEN expression was lower. Emilin1−/− mice displayed enhanced lymphangiogenesis both in the tumor and in the sentinel lymph nodes. Accordingly, tumor growth and lymph node metastasis of transplanted syngenic tumors were also increased in Emilin1−/− mice. In vitro transmigration assays through lymphatic endothelial cells showed that EMILIN1 deficiency greatly facilitated tumor cell trafficking. Overall, these data established that EMILIN1 exerts a protective role in tumor growth, in tumor lymphatic vessel formation, as well as in metastatic spread to lymph nodes and reinforced the importance of its presence in the microenvironment to determine the tumor phenotype. Cancer Prev Res; 5(9); 1131–43. ©2012 AACR.
Operator Versus Core Laboratory Assessment of Angiographic Reperfusion Markers in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction
Authors: Brener Sorin J. , Cristea Ecaterina , Lansky Alexandra J. , Fahy Martin , Mehran Roxana , Stone Gregg W. 
Published: July 2012

Background—
Thrombolysis In Myocardial Infarction (TIMI) flow and Myocardial Blush Grade (MBG) are important prognostic indicators before and after primary percutaneous coronary intervention (PCI) in ST-segment–elevation myocardial infarction; however, the concordance and relative prognostic utility of operator (Op) versus angiography core laboratory (ACL) assessed TIMI flow and MBG are unknown.

Methods and Results—

Baseline and final Op and ACL TIMI flow and MBG assessment were compared from the Harmonizing Outcomes with RevascularIZatiON and Stents in AMI trial in 3345 patients undergoing primary PCI using Cohen’s
κ
coefficient.
κ
Was highest for pre-PCI TIMI flow (0.51, representing moderate agreement) and lowest for post-PCI MBG (0.20, representing fair agreement). Discordance between Op and ACL for final TIMI flow (0 to 2 versus 3) occurred in 12.9% of patients and for final MBG (0 to 1 versus 2 to 3) in 22.4%. Among 415 patients with final TIMI flow 0 to 2 by ACL, Op scoring was TIMI flow 3 in 267 (64.3%). Similarly, among 706 patients with final MBG 0 to 1 by ACL, 563 (79.7%) were classified as MBG 2 to 3 by Op. Post-PCI TIMI 3 flow and MBG 2 to 3 strongly correlated with 3-year survival, as assessed by both Op and ACL (
P
<0.0001). Mortality was intermediate in patients in whom ACL and Op were discordant, without marked prognostic differences between the discordant groups.

Conclusions—
Op and ACL assessment of angiographic markers of reperfusion in ST-segment–elevation myocardial infarction demonstrates fair to moderate agreement. Op tended to favorably grade unfavorable ACL results. Nonetheless, both Op and ACL assessment of reperfusion strongly inform prediction of 3-year mortality.
Near-Term Fetal Hypoxia–Ischemia in Rabbits
Authors: Drobyshevsky Alexander , Derrick Matthew , Luo Kehuan , Zhang Li-Qun , Wu Yi-Ning , Takada Silvia Honda , Yu Lei , Tan Sidhartha 
Published: July 2012

Background and Purpose—
The pattern of antenatal brain injury varies with gestational age at the time of insult. Deep brain nuclei are often injured at older gestational ages. Having previously shown postnatal hypertonia after preterm fetal rabbit hypoxia–ischemia, the objective of this study was to investigate the causal relationship between the dynamic regional pattern of brain injury on MRI and the evolution of muscle tone in the near-term rabbit fetus.

Methods—
Serial MRI was performed on New Zealand white rabbit fetuses to determine equipotency of fetal hypoxia–ischemia during uterine ischemia comparing 29 days gestation (E29, 92% gestation) with E22 and E25. E29 postnatal kits at 4, 24, and 72 hours after hypoxia–ischemia underwent T2- and diffusion-weighted imaging. Quantitative assessments of tone were made serially using a torque apparatus in addition to clinical assessments.

Results—
Based on the brain apparent diffusion coefficient, 32 minutes of uterine ischemia was selected for E29 fetuses. At E30, 58% of the survivors manifested hind limb hypotonia. By E32, 71% of the hypotonic kits developed dystonic hypertonia. Marked and persistent apparent diffusion coefficient reduction in the basal ganglia, thalamus, and brain stem was predictive of these motor deficits.

Conclusions—
MRI observation of deep brain injury 6 to 24 hours after near-term hypoxia–ischemia predicts dystonic hypertonia postnatally. Torque-displacement measurements indicate that motor deficits in rabbits progressed from initial hypotonia to hypertonia, similar to human cerebral palsy, but in a compressed timeframe. The presence of deep brain injury and quantitative shift from hypo- to hypertonia may identify patients at risk for developing cerebral palsy.
Statin Use and Microbleeds in Patients With Spontaneous Intracerebral Hemorrhage
Authors: Haussen Diogo C. , Henninger Nils , Kumar Sandeep , Selim Magdy 
Published: July 2012

Background and Purpose—
Statins have been associated with increased risk of intracerebral hemorrhage (ICH), particularly in elderly patients with previous ICH. Recurrent ICH in the elderly is often related to cerebral amyloid angiopathy. Therefore, we investigated whether statin use is associated with increased prevalence and severity of microbleeds (MB), particularly cortico-subcortical microbleeds (csMB), which are frequently observed in cerebral amyloid angiopathy.

Methods—
We studied 163 consecutive patients with spontaneous ICH who underwent magnetic resonance imaging within 30 days of presentation. We retrieved clinical information and analyzed magnetic resonance imaging for the presence, location, and number of MB, which were divided into csMB or other (other MB). We performed group comparisons stratified by statin use and by the presence vs absence of any MB (csMB and/or other MB) or csMB alone.

Results—

Sixty-four percent had lobar ICH. Overall, 53% had microbleeds and 39% had csMB. Statin users were older, had significantly lower cholesterol and low-density lipoprotein levels, and higher prevalence of hypertension, diabetes, dyslipidemia, and antiplatelet use. The prevalence and number of other MB were similar in statin-treated and statin-untreated individuals. However, more statin-treated patients had csMB (57% vs 33%;
P
=0.007), with almost twice as many lesions (4.6±11.3 vs 2.4±8.0;
P
=0.007) compared with untreated patients. Age and statin use were independently associated with both the presence and increased number of MB (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.00–1.05;
P
=0.01 and OR, 2.72; 95% CI. 1.02–7.22;
P
=0.04, respectively) and csMB (OR, 1.03; 95% CI, 1.00–1.06;
P
=0.01 and OR, 4.15; 95% CI, 1.54–11.20;
P
<0.01) in multivariate analyses.

Conclusions—
Statin use in patients with ICH is independently associated with MB, especially csMB. Future studies are needed to confirm our findings and to investigate whether csMB can serve as a surrogate marker for ICH risk in statin-treated patients.
A Pentapeptide Monocyte Locomotion Inhibitory Factor Protects Brain Ischemia Injury by Targeting the eEF1A1/Endothelial Nitric Oxide Synthase Pathway
Authors: Zhang Yuefan , Chen Jun , Li Fan , Li Dong , Xiong Qinhui , Lin Yang , Zhang Dazhi , Wang Xiao-Fan , Yang Pengyuan , Rui Yao-Cheng 
Published: July 2012

Background and Purpose—

Ischemic stroke is a major cause of death worldwide but lacks viable treatment or treatment targets. Monocyte locomotion inhibitory factor (MLIF) is a small heat-stable pentapeptide produced by
Entamoeba histolytica
in axenic culture, which is supposed to protect the brain from ischemic injury; the mechanism, however, remains unknown. In this study, we further investigated the mechanism underlying the protective role of MLIF in brain ischemia.

Methods—
A middle cerebral artery occlusion model in rats was used for detecting the effect of MLIF in the brain ischemia in vivo. To identify targets of MLIF in brain endothelial cells, we performed immunoprecipitation of biotin-conjugated MLIF and mass spectrometry.

Results—
MLIF can protect the brain from ischemic injury in vivo, yielding decreased ischemic volume, prolonged survival, and improved neurological outcome. In vitro studies showed that MLIF displayed protective effects through inhibition of expression of pathological inflammatory adhesion molecules and enhancing endothelial nitric oxide synthase expression and nitric oxide release in the cerebrovascular endothelium. The target screening experiments demonstrated binding of MLIF to the ribosomal protein translation elongation factor eEF1A1. MLIF enhanced endothelial nitric oxide synthase expression through stabilization of endothelial nitric oxide synthase mRNA, and eEF1A1 was shown to be necessary for this enhanced expression. Knockdown of eEF1A1 or inhibition of endothelial nitric oxide synthase attenuated MLIF-mediated inhibition of adhesion molecule expression.

Conclusions—
In this study, we identified a new potential pharmacologically targetable mechanism underlying MLIF's protective effects in brain ischemia through the eEF1A1/endothelial nitric oxide synthase pathway.
Protein polymer hydrogels: Effects of endotoxin on biocompatibility
Authors: Beenken-Rothkopf Liese N , Karfeld-Sulzer Lindsay S , Zhang Xiaomin , Kissler Hermann , Michie Sara A , Kaufman Dixon B , Fontaine Magali J , Barron Annelise E 
Published: July 2012

Protein polymer-based hydrogels have shown potential for tissue engineering applications, but require biocompatibility testing for in vivo use. Enzymatically crosslinked protein polymer-based hydrogels were tested in vitro and in vivo to evaluate their biocompatibility. Endotoxins present in the hydrogel were removed by Trition X-114 phase separation. The reduction of endotoxins decreased TNF-α production by a macrophage cell line in vitro; however, significant inflammatory response was still present compared to collagen control gels. A branched PEG molecule and dexamethasone were added to the hydrogel to reduce the response. In vitro testing showed a decrease in the TNF-α levels with the addition of dexamethasone. In vivo implantations into the epididymal fat pad of C57/BL6 mice, however, indicated a decreased inflammatory mediated immune response with a hydrogel treated with both PEGylation and endotoxin reduction. This study demonstrates the importance of endotoxin testing and removal in determining the biocompatibility of biomaterials.
Distinct features between longitudinally extensive transverse myelitis presenting with and without anti-Aquaporin 4 antibodies
Authors: Chang K-H , Lyu R-K , Chen C-M , Wu Y-R , Chang H-S , Huang C-C , Kuo H-C , Chu C-C , Hsu W-C , Ro L-S 
Published: July 2012

Objectives: Longitudinally extensive transverse myelitis (LETM) with spinal cord lesions spanning three or more vertebral segments is a key feature of neuromyelitis optica (NMO). However, the role of anti-aquaporin 4 (anti-AQP4) antibody, a sensitive biomarker of NMO, in the conversion of LETM to NMO remains uncertain. Methods: Thirty first-ever LETM patients were retrospectively analysed and divided into two groups according to the presence of anti-AQP4 antibodies. Results: Eighteen (60%) patients presented with anti-AQP4 antibodies. Fifteen (83.33%) anti-AQP4 (+) LETM patients converted to NMO, while only three of 12 (25%, p = 0.002) anti-AQP4 (-) LETM patients progressed to NMO, over a mean follow-up period of 5.63 years. Seven (38.89%) anti-AQP4 (+) and one (8.33%) anti-AQP4 (-) LETM patients received interferon-β1a treatment, respectively. Anti-AQP4 (+) LETM patients demonstrated a higher immunogamma globulin (IgG) index (0.68 ± 0.43 versus 0.47 ± 0.19, p = 0.018), annual relapse rate (0.72 ± 0.31 versus 0.42 ± 0.17, p = 0.01) and Kurtzke Expanded Disability Status Scale (4.28 ± 2.22 versus 2.67 ± 2.26, p = 0.031), than anti-AQP4 (-) LETM patients. In spinal magnetic resonance imaging (MRIs), more than half (58.33%) of the anti-AQP4 (+) LETM patients were observed to have central grey matter-predominant involvement in the axial view, while peripheral white matter-predominant involvement (51.85%) was the most common pattern observed in the anti-AQP4 (-) LETM patients. Conclusion: Anti-AQP4 (+) LETM demonstrated a high conversion rate to NMO (83.33%), suggesting that anti-AQP4 (+) LETM may represent an early, isolated syndrome of NMO spectrum disorder. The greater number of patients receiving interferon-β treatment in anti-AQP4 (+) LETM may contribute to its high annual relapse rate.
Effectiveness and Safety of a Multicenter Extension and Retreatment Trial of Gel-200 in Patients with Knee Osteoarthritis
Authors: Strand V. , Baraf H.S.B. , Lavin P.T. , Lim S. , Hosokawa H. 
Published: July 2012

Objective: To assess the continued effectiveness and safety of Gel-200 following observation and open-label retreatment in an extension protocol following a randomized, double-blind, phosphate buffered saline (PBS)-controlled trial (initial treatment trial). Design: Patients who completed initial blinded treatment were allowed to enroll into this extension protocol that permitted retreatment with Gel-200 when eligibility criteria were met. Retreatment was administered with a Gel-200 injection, without knowledge of initial treatment assignment (Gel-200 or PBS). Retreated patients were followed for up to 13 weeks. In the extension phase, durability of response following the first injection was analyzed by time to retreatment eligibility. During separate extension and retreatment phases, responses were assessed by WOMAC pain, stiffness, and physical function subscores, total score, and global assessments of disease activity (patient, physician) as well as safety of Gel-200. Results: In the extension phase, time-to-event analyses through 26 weeks following the initial injection showed statistically significantly longer times to retreatment in patients receiving Gel-200 compared with PBS ( P < 0.05). Retreatment with Gel-200, e.g., a second injection, resulted in statistically significant improvements from retreatment baseline in all outcome measures ( P < 0.0001). The incidence and type of adverse events after retreatment were comparable to those observed following initial injection of Gel-200 without allergic reactions, including “pseudosepsis” or unanticipated treatment-related serious adverse events. Conclusions: These data demonstrate that a single injection of Gel-200 resulted in durable effectiveness through 26 weeks and that repeated treatment with Gel-200 relieved symptomatic osteoarthritis with a favorable safety profile.