bluuebunny/crossref_metadata_2025 huggingface dataset:
Purinergic Mechanosensory Transduction and Visceral Pain
Authors: Burnstock Geoffrey
Published: December 2009

In this review, evidence is presented to support the hypothesis that mechanosensory transduction occurs in tubes and sacs and can initiate visceral pain. Experimental evidence for this mechanism in urinary bladder, ureter, gut, lung, uterus, tooth-pulp and tongue is reviewed. Potential therapeutic strategies are considered for the treatment of visceral pain in such conditions as renal colic, interstitial cystitis and inflammatory bowel disease by agents that interfere with mechanosensory transduction in the organs considered, including P2X3 and P2X2/3 receptor antagonists that are orally bioavailable and stable in vivo and agents that inhibit or enhance ATP release and breakdown.
A new definition of burnout syndrome based on Farber's proposal
Authors: Montero-Marín Jesús , García-Campayo Javier , Mera Domingo Mosquera , del Hoyo Yolanda López
Published: December 2009

Background

Although diverse definitions have been construed for burnout syndrome, most authors consider it to be a single phenomenon, the result of chronic work-related stress. However, in order to enable specific intervention strategies to be adopted, it is first necessary to establish different profiles for the syndrome. In this respect, have been proposed three burnout types ("frenetic", "underchallenged" and "worn-out"), each of which requires different means of dealing with frustration in the workplace. This study is an attempt to define and systematize the properties that characterize this typology proposal.

Methods

For this purpose, the documents considering preliminary typology were examined by means of qualitative content analysis supported by grounded theory. Semiotic analysis was then performed on the core category resulting from the previous analysis.

Results

A classification criterion, made up of three different burnout subtypes ("frenetic", "underchallenged", and "worn-out") capable of integrating the entire proposal was formulated.

Discussion

Understanding the development of burnout syndrome, as a succession of stages characterized by the progressive diminishing of dedication to work, could serve for the establishment of specific therapies and for the prevention of the syndrome.
Gastro-tracheal fistula - unusual and life threatening complication after esophagectomy for cancer: a case report
Authors: Nardella Jane E , Van Raemdonck Dirk , Piessevaux Hubert , Deprez Pierre , Droissart Raphaël , Staudt Jean-Pierre , Heuker David , van Vyve Etienne
Published: December 2009

Background

A gastro-tracheal fistula following esophagectomy for cancer is a rare but potentially lethal complication. We report the successful surgical closure after failed endoscopic treatment, of a gastro-tracheal fistula following esophago-gastrectomy for cancer after induction chemo-radiotherapy.

Case presentation

A 58 year-old male patient presented with a distal third uT3N1 carcinoma of the esophagus. After induction chemo-radiotherapy, he underwent an esophago-gastrectomy with radical lymphadenectomy and reconstruction by gastric pull-up. Immediate postoperative outcome was uneventful. On the 15th postoperative day however, our patient was readmitted in the Intensive Care Unit with severe bilateral basal pneumonia. Three days later a gastro-tracheal fistula was diagnosed upon gastroscopy and bronchoscopy. His good general condition allowed for an endoscopic primary approach which consisted in the insertion of a covered stent in the trachea along with clipping and glueing of the gastric fistular orifice. Two attempts proved unsuccessful.

Conclusion

After several weeks of conservative measures, surgical re-intervention through a right thoracotomy with transection of the fistula and closure by primary interrupted sutures of both fistular orifices along with intercostal muscle flap interposition led to excellent patient outcome. Oral feeding was started and our patient was discharged.
Wear debris pseudotumor following total knee arthroplasty: a case report
Authors: Mavrogenis Andreas F , Nomikos George N , Sakellariou Vasileios I , Karaliotas George I , Kontovazenitis Panayiotis , Papagelopoulos Panayiotis J
Published: December 2009

Introduction

In patients who have undergone a total joint replacement, any mass occurring in or adjacent to the joint needs thorough investigation and a wear debris-induced cyst should be suspected.

Case presentation

An 81-year-old man presented with a painful and enlarging mass at the popliteal fossa and calf of his right knee. He had had a total right knee replacement seven years previously. Plain radiographs showed narrowing of the medial compartment. Magnetic resonance imaging showed a cystic lesion at the postero-medial aspect of the knee joint mimicking popliteal cyst or soft tissue sarcoma. Fine needle aspiration was non-diagnostic. A core-needle biopsy showed metallosis. Intraoperative findings revealed massive metallosis related to extensive polyethylene wear, delamination and deformation. Revision knee and patella arthroplasty was carried out after a thorough debridement of the knee joint.

Conclusion

Long-term follow-up is critical for patients with total joint replacement for early detection of occult polyethylene wear and prosthesis loosening. In these cases, revision arthroplasty may provide a satisfactory knee function.
Invasive thyroglossal duct cyst papillary carcinoma: a case report
Authors: Aghaghazvini Leila , Mazaher Habib , Sharifian Hashem , Aghaghazvini Shirin , Assadi Majid
Published: December 2009

Introduction

A thyroglossal duct cyst is the most common congenital anomaly of the thyroid gland and midline masses in childhood (70% abnormality in childhood, 7% in adult). Carcinomas arising from a thyroglossal duct cyst are rare (only 1% of thyroglossal duct cyst cases) and characterized by relatively non-aggressive behavior and rare lymphatic spread. They are also diagnosed mostly during the third and fourth decades of life. About 85% to 92% of all thyroglossal duct cyst carcinomas are papillary carcinomas.

Case presentation

We present the case of a 44-year-old Iranian woman with Cacausian ethnicity with a painless anterior neck mass that appeared gradually over three months. She had a history of frequent painful swelling of the anterior part of her neck, which subsided with antibiotic therapy. Thyroid functional tests were normal and a thyroid scinitigraphy showed a cold nodule in the left lobe of her thyroid. A computed tomography scan revealed a large, heterogeneous enhancing soft tissue mass with cystic components in the midline of the anterior neck space. This extended from the base of the tongue,(completely separated from its muscles, to the inferior aspect of the thyroid gland and showed the destruction of the hyoid bone and the thyroid cartilage. The diagnosis of a thyroglossal duct cyst with malignant transformation was maintained. A fine needle aspiration revealed papillary carcinoma.

Conclusion

This patient's case is presented because of its rare, aggressive, and invasive nature and rare and unusual manifestation, as well as its rapid increase in size, the destruction of the hyoid bone, chondrolysis of the thyroid cartilage, lymph adenopathy and the existence of a cold nodule in the thyroid gland.
DNA microarray profiling of genes differentially regulated by the histone deacetylase inhibitors vorinostat and LBH589 in colon cancer cell lines
Authors: LaBonte Melissa J , Wilson Peter M , Fazzone William , Groshen Susan , Lenz Heinz-Josef , Ladner Robert D
Published: December 2009

Background

Despite the significant progress made in colon cancer chemotherapy, advanced disease remains largely incurable and novel efficacious chemotherapies are urgently needed. Histone deacetylase inhibitors (HDACi) represent a novel class of agents which have demonstrated promising preclinical activity and are undergoing clinical evaluation in colon cancer. The goal of this study was to identify genes in colon cancer cells that are differentially regulated by two clinically advanced hydroxamic acid HDACi, vorinostat and LBH589 to provide rationale for novel drug combination partners and identify a core set of HDACi-regulated genes.

Methods

HCT116 and HT29 colon cancer cells were treated with LBH589 or vorinostat and growth inhibition, acetylation status and apoptosis were analyzed in response to treatment using MTS, Western blotting and flow cytometric analyses. In addition, gene expression was analyzed using the Illumina Human-6 V2 BeadChip array and Ingenuity®Pathway Analysis.

Results

Treatment with either vorinostat or LBH589 rapidly induced histone acetylation, cell cycle arrest and inhibited the growth of both HCT116 and HT29 cells. Bioinformatic analysis of the microarray profiling revealed significant similarity in the genes altered in expression following treatment with the two HDACi tested within each cell line. However, analysis of genes that were altered in expression in the HCT116 and HT29 cells revealed cell-line-specific responses to HDACi treatment. In addition a core cassette of 11 genes modulated by both vorinostat and LBH589 were identified in both colon cancer cell lines analyzed.

Conclusion

This study identified HDACi-induced alterations in critical genes involved in nucleotide metabolism, angiogenesis, mitosis and cell survival which may represent potential intervention points for novel therapeutic combinations in colon cancer. This information will assist in the identification of novel pathways and targets that are modulated by HDACi, providing much-needed information on HDACi mechanism of action and providing rationale for novel drug combination partners. We identified a core signature of 11 genes which were modulated by both vorinostat and LBH589 in a similar manner in both cell lines. These core genes will assist in the development and validation of a common gene set which may represent a molecular signature of HDAC inhibition in colon cancer.
From HIV diagnosis to treatment: evaluation of a referral system to promote and monitor access to antiretroviral therapy in rural Tanzania
Authors: Nsigaye Ray , Wringe Alison , Roura Maria , Kalluvya Samuel , Urassa Mark , Busza Joanna , Zaba Basia
Published: December 2009

Background

Individuals diagnosed with HIV in developing countries are not always successfully linked to onward treatment services, resulting in missed opportunities for timely initiation of antiretroviral therapy, or prophylaxis for opportunistic infections. In collaboration with local stakeholders, we designed and assessed a referral system to link persons diagnosed at a voluntary counselling and testing (VCT) clinic in a rural district in northern Tanzania with a government‐run HIV treatment clinic in a nearby city.

Methods

Two‐part referral forms, with unique matching numbers on each side were implemented to facilitate access to the HIV clinic, and were subsequently reconciled to monitor the proportion of diagnosed clients who registered for these services, stratified by sex and referral period. Delays between referral and registration at the HIV clinic were calculated, and lists of non‐attendees were generated to facilitate tracing among those who had given prior consent for follow up.

Transportation allowances and a “community escort” from a local home‐based care organization were introduced for patients attending the HIV clinic, with supportive counselling services provided by the VCT counsellors and home‐based care volunteers. Focus group discussions and in‐depth interviews were conducted with health care workers and patients to assess the acceptability of the referral procedures.

Results

Referral uptake at the HIV clinic averaged 72% among men and 66% among women during the first three years of the national antiretroviral therapy (ART) programme, and gradually increased following the introduction of the transportation allowances and community escorts, but declined following a national VCT campaign. Most patients reported that the referral system facilitated their arrival at the HIV clinic, but expressed a desire for HIV treatment services to be in closer proximity to their homes. The referral forms proved to be an efficient and accepted method for assessing the effectiveness of the VCT clinic as an entry point for ART.

Conclusion

The referral system reduced delays in seeking care, and enabled the monitoring of access to HIV treatment among diagnosed persons. Similar systems to monitor referral uptake and linkages between HIV services could be readily implemented in other settings.
India‐US collaboration to prevent adolescent HIV infection: the feasibility of a family‐based HIV‐prevention intervention for rural Indian youth
Authors: Soletti Asha Banu , Guilamo‐Ramos Vincent , Burnette Denise , Sharma Shilpi , Bouris Alida
Published: December 2009

Background

Despite the centrality of family in Indian society, relatively little is known about family‐based communication concerning sexual behaviour and HIV/AIDS in rural Indian families. To date, very few family‐based adolescent HIV‐prevention interventions have been developed for rural Indian youth. This study conducted formative research with youth aged 14 to18 years and their parents in order to assess the feasibility of conducting a family‐based HIV‐prevention intervention for rural Indian adolescents.

Methods

Eight focus groups were conducted (n = 46) with mothers, fathers, adolescent females and adolescent males (two focus groups were held for each of the four groups). All focus groups consisted of same‐gender participants. Adolescents aged 14 to18 years old and their parents were recruited from a tribal community in rural Maharashtra, India. Focus group transcripts were content analyzed to identify themes related to family perceptions about HIV/AIDS and participation in a family‐based intervention to reduce adolescent vulnerability to HIV infection.

Results

Six primary thematic areas were identified: (1) family knowledge about HIV/AIDS; (2) family perceptions about adolescent vulnerability to HIV infection; (3) feasibility of a family‐based programme to prevent adolescent HIV infection; (4) barriers to participation; (5) recruitment and retention strategies; and (6) preferred content for an adolescent HIV prevention intervention.

Conclusion

Despite suggestions that family‐based approaches to preventing adolescent HIV infection may be culturally inappropriate, our results suggest that a family‐based intervention to prevent adolescent HIV infection is feasible if it: (1) provides families with comprehensive HIV prevention strategies and knowledge; (2) addresses barriers to participation; (3) is adolescent friendly, flexible and convenient; and (4) is developmentally and culturally appropriate for rural Indian families.
Measurement of tissue cortisol levels in patients with severe burns: a preliminary investigation
Authors: Cohen Jeremy , Deans Renae , Dalley Andrew , Lipman Jeff , Roberts Michael S , Venkatesh Bala
Published: December 2009

Introduction

The assessment of adrenal function in critically ill patients is problematic, and there is evidence to suggest that measurement of tissue glucocorticoid activity may be more useful than estimation of plasma cortisol concentrations. Interstitial cortisol concentrations of cortisol represent the available pool of glucocorticoids able to enter the cell and bind to the glucocorticoid receptor. However the concentrations of plasma cortisol may not accurately reflect interstitial concentrations. We elected to perform a preliminary study into the feasibility of measuring interstitial cortisol by microdialysis, and to investigate the relationship between total plasma cortisol, free plasma cortisol and interstitial cortisol in patients with severe burns.

Methods

A prospective observational study carried out in a tertiary intensive care unit. Ten adult patients with a mean total burn surface area of 48% were studied. Interstitial cortisol was measured by microdialysis from patient-matched burnt and non-burnt tissue and compared with that of 3 healthy volunteers. Plasma sampling for estimations of total and free cortisol concentrations was performed concurrently.

Results

In the burn patients, mean total plasma and free plasma cortisol concentrations were 8.8 +/- 3.9, and 1.7 +/- 1.1 mcg/dL, (p < 0.001), respectively. Mean subcutaneous microdialysis cortisol concentrations in the burn and non-burn tissue were 0.80 +/- 0.31 vs 0.74 +/- 0.41 mcg/dL (p = 0.8), respectively, and were significantly elevated over the mean subcutaneous microdialysis cortisol concentrations in the healthy volunteers. There was no significant correlation between total plasma or free plasma and microdialysis cortisol concentrations. Plasma free cortisol was better correlated with total burn surface area than total cortisol.

Conclusions

In this preliminary study, interstitial cortisol concentrations measured by microdialysis in burnt and non-burnt skin from patients with severe thermal injury are significantly elevated over those from healthy volunteers. Plasma estimations of cortisol do not correlate with the microdialysis levels, raising the possibility that plasma cortisol may be an unreliable guide to tissue cortisol activity.
Angiotensin II in experimental hyperdynamic sepsis
Authors: Wan Li , Langenberg Christoph , Bellomo Rinaldo , May Clive N
Published: December 2009

Introduction

Angiotensin II (Ang II) is a potential vasopressor treatment for hypotensive hyperdynamic sepsis. However, unlike other vasopressors, its systemic, regional blood flow and renal functional effects in hypotensive hyperdynamic sepsis have not been investigated.

Methods

We performed an experimental randomised placebo-controlled animal study. We induced hyperdynamic sepsis by the intravenous administration of live E. coli in conscious ewes after chronic instrumentation with flow probes around the aorta and the renal, mesenteric, coronary and iliac arteries. We allocated animals to either placebo or angiotensin II infusion titrated to maintain baseline blood pressure.

Results

Hyperdynamic sepsis was associated with increased renal blood flow (from 292 +/- 61 to 397 +/- 74 ml/min), oliguria and a decrease in creatinine clearance (from 88.7 +/- 19.6 to 47.7 +/- 21.0 ml/min, P < 0.0001). Compared to placebo, Ang II infusion restored arterial pressure but reduced renal blood flow (from 359 +/- 81 ml/min to 279 +/- 86 ml/min; P < 0.0001). However, despite the reduction in renal blood flow, Ang II increased urine output approximately 7-fold (364 +/- 272 ml/h vs. 48 +/- 18 ml/h; P < 0.0001), and creatinine clearance by 70% (to 80.6 +/- 20.7 ml/min vs.46.0 +/- 26 ml/min; P < 0.0001). There were no major effects of Ang II on other regional blood flows.

Conclusions

In early experimental hypotensive hyperdynamic sepsis, intravenous angiotensin II infusion decreased renal blood while inducing a marked increase in urine output and normalizing creatinine clearance.
A Laboratory-intensive Course on RNA Interference and Model Organisms
Authors: Miller Joanna A. , Witherow D. Scott , Carson Susan
Published: December 2009

RNA interference (RNAi) is a powerful method to silence gene expression in a variety of organisms and is generating interest not only as a useful tool for research scientists but also as a novel class of therapeutics in clinical trials. Here, we report that undergraduate and graduate students with a basic molecular biology background were able to demonstrate conceptual knowledge and technical skills for using RNAi as a research tool upon completion of an intensive 8-wk RNAi course with a 2-h lecture and 5-h laboratory per week. Students were instructed on design of RNAi experiments in model organisms and perform multiweek laboratory sessions based on journal articles read and discussed in class. Using Nicotiana benthamiana, Caenorhabditis elegans, and mammalian cell culture, students analyzed the extent of silencing using both qualitative assessment of phenotypic variations and quantitative measurements of RNA levels or protein levels. We evaluated the course over two semesters, each with a separate instructor. In both semesters, we show students met expected learning outcomes as demonstrated by successful laboratory experiment results, as well as positive instructor assessments of exams and lab reports. Student self-assessments revealed increased confidence in conceptual knowledge and practical skills. Our data also suggest that the course is adaptable to different instructors with varying expertise.
Effectiveness of a Cloning and Sequencing Exercise on Student Learning with Subsequent Publication in the National Center for Biotechnology Information GenBank
Authors: Lau Joann M. , Robinson David L.
Published: December 2009

With rapid advances in biotechnology and molecular biology, instructors are challenged to not only provide undergraduate students with hands-on experiences in these disciplines but also to engage them in the “real-world” scientific process. Two common topics covered in biotechnology or molecular biology courses are gene-cloning and bioinformatics, but to provide students with a continuous laboratory-based research experience in these techniques is difficult. To meet these challenges, we have partnered with Bio-Rad Laboratories in the development of the “Cloning and Sequencing Explorer Series,” which combines wet-lab experiences (e.g., DNA extraction, polymerase chain reaction, ligation, transformation, and restriction digestion) with bioinformatics analysis (e.g., evaluation of DNA sequence quality, sequence editing, Basic Local Alignment Search Tool searches, contig construction, intron identification, and six-frame translation) to produce a sequence publishable in the National Center for Biotechnology Information GenBank. This 6- to 8-wk project-based exercise focuses on a pivotal gene of glycolysis (glyceraldehyde-3-phosphate dehydrogenase), in which students isolate, sequence, and characterize the gene from a plant species or cultivar not yet published in GenBank. Student achievement was evaluated using pre-, mid-, and final-test assessments, as well as with a survey to assess student perceptions. Student confidence with basic laboratory techniques and knowledge of bioinformatics tools were significantly increased upon completion of this hands-on exercise.
Cognitive functioning in schizophrenia, schizoaffective disorder and affective psychoses: meta-analytic study
Authors: Bora Emre , Yucel Murat , Pantelis Christos
Published: December 2009

Background

Cognitive functioning in affective psychosis and schizoaffective disorder is much less studied compared with schizophrenia.

Aims

To quantitatively undertake a meta-analysis of the available data that directly compares cognitive functioning across schizophrenia, schizoaffective disorder and affective psychosis.

Method

Following a thorough literature review, 31 studies that compared the performances of people with schizophrenia (1979 participants) with that of those with affective psychosis or schizoaffective disorder (1314 participants) were included. To determine the effect of demographic and clinical confounders, meta-regression and subgroup analyses were conducted.

Results

In 6 of 12 cognitive domains, people with schizophrenia performed worse than people with schizoaffective disorder or affective psychosis. However, the between-group differences were small and the distribution of effect sizes showed substantial heterogeneity. The between-group differences were driven by a higher percentage of males, more severe negative symptoms and younger age at onset of illness in the schizophrenia samples.

Conclusions

Neuropsychological data do not provide evidence for categorical differences between schizophrenia and other groups. However, a subgroup of individuals with schizophrenia who have more severe negative symptoms may be cognitively more impaired than those with affective psychosis/schizoaffective disorder.
Association between extreme autistic traits and intellectual disability: insights from a general population twin study
Authors: Hoekstra R. A. , Happé F. , Baron-Cohen S. , Ronald A.
Published: December 2009

Background

Autism is associated with intellectual disability. The strength and origin of this association is unclear.

Aims

To investigate the association between extreme autistic traits and intellectual disability in children from a community-based sample and to examine whether the association can be explained by genetic factors.

Method

Children scoring in the extreme 5% on measures of autistic traits, IQ and academic achievement were selected from 7965 7/8-year-old and 3687 9-year-old twin pairs. Phenotypic associations between extreme autistic traits and intellectual disability were compared with associations among the full-range scores. Genetic correlations were estimated using bivariate DeFries–Fulker extremes analyses.

Results

Extreme autistic traits were modestly related to intellectual disability; this association was driven by communication problems characteristic of autism. Although this association was largely explained by genetic factors, the genetic correlation between autistic traits and intellectual disability was only modest.

Conclusions

Extreme autistic traits are substantially genetically independent of intellectual disability.
Genetic and environmental contributions to depression in Sri Lanka
Authors: Ball Harriet A. , Sumathipala Athula , Siribaddana Sisira H. , Kovas Yulia , Glozier Nick , McGuffin Peter , Hotopf Matthew
Published: December 2009

Background

Susceptibility to depression results from genetic and non-familially shared environmental influences in high-income, Western countries. Environments may play a different role for populations in different contexts.

Aims

To examine heritability of depression in the first large, population-based twin study in a low-income country.

Method

Lifetime depression and a broader measure of depression susceptibility (D-probe) were assessed in 3908 adult twins in Sri Lanka (the CoTASS study).

Results

There were gender differences for the broad definition (D-probe), with a higher genetic contribution in females (61%) than males (4%). Results were similar for depression, but the prevalence was too low to estimate heritability for males.

Conclusions

Genetic influences on depression in women appear to be at least as strong in this Sri Lankan sample as in higher-income countries. Conclusions are less clear for men but suggest a larger role for environments rather than genes. The nature as well as the magnitude of environmental influences may also differ across populations.
High-potency cannabis and the risk of psychosis
Authors: Di Forti Marta , Morgan Craig , Dazzan Paola , Pariante Carmine , Mondelli Valeria , Marques Tiago Reis , Handley Rowena , Luzi Sonija , Russo Manuela , Paparelli Alessandra , Butt Alexander , Stilo Simona A. , Wiffen Ben , Powell John , Murray Robin M.
Published: December 2009

Background

People who use cannabis have an increased risk of psychosis an effect attributed to the active ingredient δ9-tetrahydrocannabinol (Δ9-THC). There has recently been concern over an increase in the concentration of Δ9-THC in the cannabis available in many countries.

Aims

To investigate whether people with a first episode of psychosis were particularly likely to use high-potency cannabis.

Method

We collected information on cannabis use from 280 cases presenting with a first episode of psychosis to the South London & Maudsley National Health Service (NHS) Foundation Trust, and from 174 healthy controls recruited from the local population.

Results

There was no significant difference between cases and controls in whether they had ever taken cannabis, or age at first use. However, those in the cases group were more likely to be current daily users (OR = 6.4) and to have smoked cannabis for more than 5 years (OR = 2.1). Among those who used cannabis, 78% of the cases group used high-potency cannabis (sinsemilla, ‘skunk’) compared with 37% of the control group (OR 6.8).

Conclusions

The finding that people with a first episode of psychosis had smoked higher-potency cannabis, for longer and with greater frequency, than a healthy control group is consistent with the hypothesis that Δ9-THC is the active ingredient increasing risk of psychosis. This has important public health implications, given the increased availability and use of high-potency cannabis.
Meta-Analysis of Breast Cancer Outcomes in Adjuvant Trials of Aromatase Inhibitors Versus Tamoxifen
Authors: Dowsett Mitch , Cuzick Jack , Ingle Jim , Coates Alan , Forbes John , Bliss Judith , Buyse Marc , Baum Michael , Buzdar Aman , Colleoni Marco , Coombes Charles , Snowdon Claire , Gnant Michael , Jakesz Raimund , Kaufmann Manfred , Boccardo Francesco , Godwin Jon , Davies Christina , Peto Richard
Published: December 2009

Purpose

To conduct meta-analyses of randomized trials of aromatase inhibitors (AIs) compared with tamoxifen either as initial monotherapy (cohort 1) or after 2 to 3 years of tamoxifen (cohort 2).

Materials and Methods

Data submitted to the Early Breast Cancer Trialists' Collaborative Group were used in separate meta-analyses of two cohorts. Primary analyses involve postmenopausal women with tumors reported to be estrogen receptor positive. Log-rank P values are two-sided.

Results

Cohort 1 comprised 9,856 patients with a mean of 5.8 years of follow-up. At 5 years, AI therapy was associated with an absolute 2.9% (SE = 0.7%) decrease in recurrence (9.6% for AI v 12.6% for tamoxifen; 2P < .00001) and a nonsignificant absolute 1.1% (SE = 0.5%) decrease in breast cancer mortality (4.8% for AI v 5.9% for tamoxifen; 2P = .1). Cohort 2 comprised 9,015 patients with a mean of 3.9 years of follow-up. At 3 years from treatment divergence (ie, approximately 5 years after starting hormonal treatment), AI therapy was associated with an absolute 3.1% (SE = 0.6%) decrease in recurrence (5.0% for AI v 8.1% for tamoxifen since divergence; 2P < .00001) and an absolute 0.7% (SE = 0.3%) decrease in breast cancer mortality (1.7% for AI v 2.4% for tamoxifen since divergence; 2P = .02). There was no convincing heterogeneity in the proportional recurrence reduction with respect to age, nodal status, tumor grade, or progesterone receptor status and no indication of an increase in nonbreast deaths with AIs in either cohort.

Conclusion

AIs produce significantly lower recurrence rates compared with tamoxifen, either as initial monotherapy or after 2 to 3 years of tamoxifen. Additional follow-up will provide clearer information on long-term survival.
Clinical Definition of Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer
Authors: Jackman David , Pao William , Riely Gregory J. , Engelman Jeffrey A. , Kris Mark G. , Jänne Pasi A. , Lynch Thomas , Johnson Bruce E. , Miller Vincent A.
Published: December 2009

Ten percent of North American patients with non–small-cell lung cancer have tumors with somatic mutations in the gene for the epidermal growth factor receptor (EGFR). Approximately 70% of patients whose lung cancers harbor somatic mutations in exons encoding the tyrosine kinase domain of EGFR experience significant tumor regressions when treated with the EGFR tyrosine kinase inhibitors (TKIs) gefitinib or erlotinib. However, the overwhelming majority of these patients inevitably acquire resistance to either drug. Currently, the clinical definition of such secondary or acquired resistance is not clear. We propose the following criteria be used to define more precisely acquired resistance to EGFR TKIs. All patients should have the following criteria: previous treatment with a single-agent EGFR TKI (eg, gefitinib or erlotinib); either or both of the following: a tumor that harbors an EGFR mutation known to be associated with drug sensitivity or objective clinical benefit from treatment with an EGFR TKI; systemic progression of disease (Response Evaluation Criteria in Solid Tumors [RECIST] or WHO) while on continuous treatment with gefitinib or erlotinib within the last 30 days; and no intervening systemic therapy between cessation of gefitinib or erlotinib and initiation of new therapy. The relatively simple definition proposed here will lead to a more uniform approach to investigating the problem of acquired resistance to EGFR TKIs in this unique patient population. These guidelines should minimize reporting of false-positive and false-negative activity in these clinical trials and would facilitate the identification of agents that truly overcome acquired resistance to gefitinib and erlotinib.
Use of Video to Facilitate End-of-Life Discussions With Patients With Cancer: A Randomized Controlled Trial
Authors: El-Jawahri Areej , Podgurski Lisa M. , Eichler April F. , Plotkin Scott R. , Temel Jennifer S. , Mitchell Susan L. , Chang Yuchiao , Barry Michael J. , Volandes Angelo E.
Published: December 2009

Purpose

To determine whether the use of a goals-of-care video to supplement a verbal description can improve end-of-life decision making for patients with cancer.

Methods

Fifty participants with malignant glioma were randomly assigned to either a verbal narrative of goals-of-care options at the end of life (control), or a video after the same verbal narrative (intervention) in this randomized controlled trial. The video depicts three levels of medical care: life-prolonging care (cardiopulmonary resuscitation [CPR], ventilation), basic care (hospitalization, no CPR), and comfort care (symptom relief). The primary study outcome was participants' preferences for end-of-life care. The secondary outcome was participants' uncertainty regarding decision making (score range, 3 to 15; higher score indicating less uncertainty). Participants' comfort level with the video was also measured.

Results

Fifty participants were randomly assigned to either the verbal narrative (n = 27) or video (n = 23). After the verbal description, 25.9% of participants preferred life-prolonging care, 51.9% basic care, and 22.2% comfort care. In the video arm, no participants preferred life-prolonging care, 4.4% preferred basic care, 91.3% preferred comfort care, and 4.4% were uncertain (P < .0001). The mean uncertainty score was higher in the video group than in the verbal group (13.7 v 11.5, respectively; P < .002). In the intervention arm, 82.6% of participants reported being very comfortable watching the video.

Conclusion

Compared with participants who only heard a verbal description, participants who viewed a goals-of-care video were more likely to prefer comfort care and avoid CPR, and were more certain of their end-of-life decision making. Participants reported feeling comfortable watching the video.
The Different Characteristics and Geological Significance of Reduction Alteration of Sandstone-Type Uranium Deposits in Northwest Region of China
Authors: Wu Bolin , Zheng Gui , Zhang Aijia , Wang Weiyang , Qiu Xinwei , Wang Jianqiang , Hu Liang , Zhang Benhao
Published: December 2009

Based on isotope trace studies of sandstone-type uranium deposits in Dongsheng area of Ordos basin, south margin in Yili basin and Turpan-Hami basin, such as geological attitude, carbon and oxygen isotope in fluids, hydrogen and oxygen isotope, sulfur isotope in pyrite and carbon isotope in “detritus pot top gas” of mineral-bearing stratum, this paper reveals the different features of the reduction and alteration among the formation of three uranium deposits. The differences are mainly reflected on the types of organic matter and the reduction alteration scale. These differences are the main reason to cause apparent epigenetic alteration types and intensity of uranium mineralization. It is concluded that the reduction of coal bed methane dissipation from the Neopaleozoic is the main feature of Dongsheng deposit, which leads to the abroad development of green-color alteration and bleaching phenomenon. The reduction of bacteria is the main feature of Yili deposit, which leads to a small range of weaker fading alteration and much more framboidal spherules pyrited mineralization. The organic acid from dispersed coal particles in stratum is the main feature of Turpan-Hami basin deposit, which is the main reductant of the uranium deposit. According to the above-mentioned characteristics, we think that the types, characteristics, and the scale of reductant are the important factors in determining the types of uranium deposits and the differences between the scales. This recognition has an important theoretical and practical significance to research genetic types of uranium deposits and their exploration methods.
A structural analysis of the group II intron active site and implications for the spliceosome
Authors: Keating Kevin S. , Toor Navtej , Perlman Philip S. , Pyle Anna Marie
Published: December 2009

Group II introns are self-splicing, mobile genetic elements that have fundamentally influenced the organization of terrestrial genomes. These large ribozymes remain important for gene expression in almost all forms of bacteria and eukaryotes and they are believed to share a common ancestry with the eukaryotic spliceosome that is required for processing all nuclear pre-mRNAs. The three-dimensional structure of a group IIC intron was recently determined by X-ray crystallography, making it possible to visualize the active site and the elaborate network of tertiary interactions that stabilize the molecule. Here we describe the molecular features of the active site in detail and evaluate their correspondence with prior biochemical, genetic, and phylogenetic analyses on group II introns. In addition, we evaluate the structural significance of RNA motifs within the intron core, such as the major-groove triple helix and the domain 5 bulge. Having combined what is known about the group II intron core, we then compare it with known structural features of U6 snRNA in the eukaryotic spliceosome. This analysis leads to a set of predictions for the molecular structure of the spliceosomal active site.
Thermodynamic analysis of ligand binding and ligand binding-induced tertiary structure formation by the thiamine pyrophosphate riboswitch
Authors: Kulshina Nadia , Edwards Thomas E. , Ferré-D'Amaré Adrian R.
Published: December 2009

The thi-box riboswitch regulates gene expression in response to the intracellular concentration of thiamine pyrophosphate (TPP) in archaea, bacteria, and eukarya. To complement previous biochemical, genetic, and structural studies of this phylogenetically widespread RNA domain, we have characterized its interaction with TPP by isothermal titration calorimetry. This shows that TPP binding is highly dependent on Mg2+ concentration. The dissociation constant decreases from ∼200 nM at 0.5 mM Mg2+ concentration to ∼9 nM at 2.5 mM Mg2+ concentration. Binding is enthalpically driven, but the unfavorable entropy of binding decreases as Mg2+ concentration rises, suggesting that divalent cations serve to pre-organize the RNA. Mutagenesis, biochemical analysis, and a new crystal structure of the riboswitch suggest that a critical element that participates in organizing the riboswitch structure is the tertiary interaction formed between the P3 and L5 regions. This tertiary contact is distant from the TPP binding site, but calorimetric analysis reveals that even subtle mutations in L5 can have readily detectable effects on TPP binding. The thermodynamic signatures of these mutations, namely decreased favorable enthalpy of binding and small effects on entropy of binding, are consistent with the P3–L5 association contributing allosterically to TPP-induced compaction of the RNA.
A distant mirror: Memories of parents and friends across childhood and adolescence
Authors: Peterson Carole. , Bonechi Alice. , Smorti Andrea. , Tani Franca.
Published: December 2009

Memories that were easily accessible (i.e., quickly retrieved in a memory‐fluency task) of Italian university students were assessed. They were from four periods of life: preschool, elementary school, middle school, and high school/university. Half of the participants were instructed to recall only memories involving parents, and the other half memories involving friends. Across age at the time of remembered events, only memories of friends increased in frequency. For parental memories (but not friend memories), the proportion with negative affect increased over age, especially for males. There were also differences related to whether memories were episodic or generic. It was concluded that memories of different periods of childhood and adolescence can serve as a reflective mirror for developmental changes in parent–child and friendship relationships.
Earworms (stuck song syndrome): Towards a natural history of intrusive thoughts
Authors: Beaman C. Philip , Williams Tim I.
Published: December 2009

Two studies examine the experience of ‘earworms’, unwanted catchy tunes that repeat. Survey data show that the experience is widespread but earworms are not generally considered problematic, although those who consider music to be important to them report earworms as longer, and harder to control, than those who consider music as less important. The tunes which produce these experiences vary considerably between individuals but are always familiar to those who experience them. A diary study confirms these findings and also indicates that, although earworm recurrence is relatively uncommon and unlikely to persist for longer than 24 h, the length of both the earworm and the earworm experience frequently exceed standard estimates of auditory memory capacity. Active attempts to block or eliminate the earworm are less successful than passive acceptance, consistent with Wegner's theory of ironic mental control.
Retracted: It depends on how you look at it: Being versus becoming mindsets determine responses to social comparisons
Authors: Johnson Camille S. , Stapel Diederik A.
Published: December 2009

The current studies examine how focusing on evaluation of the current self (a ‘being’ mindset) or focusing on the projection of future selves (a ‘becoming mindset’) influences responses to social comparison information. The studies show that the mindset of individuals, independent of other situational variables, determines whether individuals regard targets as threatening, how targets influence self‐evaluations, and how targets affect performance on relevant tasks. The studies also show that mindsets determine what kinds of social comparison information are influential. In a becoming mindset, people are influenced mainly by information from domains that are considered mutable, whereas in a being mindset, people are influenced by information from both immutable and mutable domains.
(Looking) Back to the Future: Using Space—Time Patterns to Better Predict the Location of Street Crime
Authors: Tompson Lisa , Townsley Michael
Published: December 2009

Crime analysts attempt to identify regularities in police recorded crime data with a central view of disrupting the patterns found. One common method for doing so is hotspot mapping, focusing attention on spatial clustering as a route to crime reduction (Chainey & Ratcliffe, 2005; Clarke & Eck, 2003). Despite the widespread use of this analytical technique, evaluation tools to assess its ability to accurately predict spatial patterns have only recently become available to practitioners (Chainey, Tompson, & Uhlig, 2008). Crucially, none has examined this issue from a spatio-temporal standpoint. Given that the organisational nature of policing agencies is shift based, it is common-sensical to understand crime problems at this temporal sensitivity, so there is an opportunity for resources to be deployed swiftly in a manner that optimises prevention and detection.

This paper tests whether hotspot forecasts can be enhanced when time-of-day information is incorporated into the analysis. Using street crime data, and employing an evaluative tool called the Predictive Accuracy Index (PAI), we found that the predictive accuracy can be enhanced for particular temporal shifts, and this is primarily influenced by the degree of spatial clustering present. Interestingly, when hotspots shrank (in comparison with the all-day hotspots), they became more concentrated, and subsequently more predictable. This is meaningful in practice; for if crime is more predictable during specific time-frames, then response resources can be used intelligently to reduce victimisation.
Generating and Using Community Intelligence: The Case of Neighbourhood Policing
Authors: Bullock Karen
Published: December 2009

This paper examines the role that community-generated information plays in ‘neighbourhood policing’ — a key component of the UK police reform agenda. The neighbourhood policing agenda is concerned with the delivery of a consistent presence of dedicated neighbourhood teams which should be visible and accessible to the community. However, it also calls for the generation of community intelligence which should be used for local problem-solving and should be incorporated into National Intelligence Model (NIM) tasking. At the time of writing the principle of incorporating information generated from the public into policing intelligence and priority setting thus has strong resonance, at least at the level of rhetoric of policy and practice. It is contended that difficult questions are posed in thinking through what it means to consult with the ‘public’, the nature of community generated information and how it is translated into operational decisions and resource deployment. This paper explores the conceptual foundations of neighbourhood policing — which are found in reassurance policing, problem-oriented policing and the National Intelligence Model. It then examines the current mechanisms for generating community information, prioritising problems, and delivering responses as they are applied in neighbourhood policing. It finishes with a critical discussion of the concept and practice of generating and using community information for setting local policing priorities.
Police and the Reclamation of Public Places: A Study of MacArthur Park in Los Angeles
Authors: Sousa William H. , Kelling George L.
Published: December 2009

Throughout the 1980s and 1990s, MacArthur Park — a 40-acre public park located near downtown Los Angeles — was widely known to be one of the largest open-air drug markets in Los Angeles. The Alvarado Corridor Initiative, a police-led initiative developed in 2003, was designed to address crime and disorderly behaviour in MacArthur Park through a combination of problem-solving, order-maintenance, and situational crime prevention efforts. This paper assesses the impact of the Alvarado Corridor Initiative using information from interviews and focus groups with neighbourhood residents, business-people, police officers, and other individuals familiar with MacArthur Park. The results suggest that many of the problems in MacArthur Park have been resolved and that the park experienced a turnaround that can be linked to the implementation of the Alvarado Corridor Initiative. In assessing the effectiveness of the Alvarado Corridor Initiative, this paper also provides a commentary on the evolution of public places in the United States and the role that the police can serve in terms of helping to preserve those public places.
An Empirical Study of Intelligence Strategy Implementation
Authors: Gottschalk Petter , Gudmundsen Yngve Sommerseth
Published: December 2009

Strategy implementation suffers from a general lack of academic attention. The need for improved implementation of strategies in law enforcement and policing has been emphasised by both scholars and practitioners. Implementation is important for four reasons. First, the failure to carry out a strategy can cause lost opportunities, duplicated efforts, incompatible organisational units and wasted resources. Second, the extent to which a strategy meets its objectives is determined by implementation. Third, the lack of implementation leaves police officers dissatisfied and reluctant to continue doing strategic planning work. Finally, the lack of implementation creates problems establishing and maintaining priorities in future strategic planning. In this empirical study, implementation of intelligence strategy is studied in a causal relationship with organisation structure and organisation culture. It is found that a knowledge organisation structure has a significant positive influence on the extent of strategy implementation.