bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of early transmission of pandemic influenza in London – link with deprivation
Authors: Balasegaram Sooria , Ogilvie Flora , Glasswell Amy , Anderson Charlotte , Cleary Vivien , Turbitt Deborah , McCloskey Brian 
Published: January 2012

Please cite this paper as: Balasegaram et al. (2012) Patterns of early transmission of pandemic influenza in London – link with deprivation. Influenza and Other Respiratory Viruses 6(3), e35–e41.Background  During the early containment phase in England from April to June 2009, the national strategy for H1N1 pandemic influenza involved case investigation and treatment, and tracing and prophylaxis of contacts.Objective  To describe the relationship between early transmission of H1N1 pandemic influenza in London and age and socio‐economic status.Methods  Epidemiological data on cases of pandemic flu in London reported to the London Flu Response Centre were analysed to determine patterns of transmission.Results  There were 3487 reported cases (2202 confirmed, 1272 presumed and 14 probable) from 20 April to 28 June 2009, during the ‘containment’ period. The highest report rate of 206 per 100 000 (95% CI 195–218) was seen in primary school–age children (5−11 years) followed by 129 (95% CI 119–139) in secondary school–age children (12–18 years). Reports of cases were initially concentrated in affluent areas but overall showed a clear trend with deprivation and risk ratio of 2·32 (95% CI 1·94–2·78) between the most deprived and the least deprived.Conclusion  Early transmissions were highest amongst school‐aged children but linked with socio‐economic deprivation across all age groups.
Intermediate catheter injections in closed segments during acute stroke intervention: a cautionary note
Authors: Hui Ferdinand K , Yim John , Spiotta Alejandro M , Hussain M Shazam , Toth Gabor 
Published: January 2012

Objective and importanceIn the setting of stroke intervention, there is typically an occlusion that limits angiographic visualization of patent vasculature distal to the embolus. Certain mechanical thrombectomy paradigms include angiography of the vasculature distal to the point of occlusion in preparation for thrombectomy, typically using a microcatheter. Injections using an intermediate catheter allows for higher volume of injection at a faster rate, resulting in radically different pressure gradients.Clinical presentationsTwo patients presenting with acute ischemic stroke were treated via mechanical thrombectomy using the Penumbra 054 system. The first was a tandem occlusion with a high grade narrowing and occlusion of the internal carotid artery (ICA) origin and an ICA terminus thrombus. The second was a long segment, high volume thrombus extending from the cavernous segment to the ICA terminus.InterventionConventional access techniques were utilized to position the Penumbra 054 catheter in the ICA in both cases. Intraprocedurally, angiography through the 054 catheter within the closed segment resulted in contrast extravasation adjacent to the tentorium, originating from the communicating segment of the ICA, both of which cleared within 48 h. Due to the extravasation, the interventions were both terminated, and the infarcts went on to complete.ConclusionDuring an acute stroke, flow within large vessels is abnormal, and rapid changes in volume may result in drastic changes in pressure which may lead to extravasation. The authors recommend never performing a contrast injection through a large lumen catheter when flow may be impeded proximally and distally. Closed segment injections of large volumes at a high rate are probably at high risk for vessel injury.
Histopathology of the endophytic system and aerial shoots of Arceuthobium americanum infected by Colletotrichum gloeosporioides
Authors: Ramsfield T.D. , Shamoun S.F. , van der Kamp B.J. 
Published: January 2012

Infection of the endophytic system of Arceuthobium americanum parasitizing Pinus contorta var. latifolia by the fungus Colletotrichum gloeosporioides was assessed on naturally infected and inoculated localized dwarf mistletoe plants. Two different techniques were utilized to attempt to inoculate C. gloeosporioides into the endophytic system: the fungus was applied as Stabileze formulated product onto cut A. americanum shoots and as a mycelial plug to wounded A. americanum infected host branches. The fungus was cultured from infected shoots and the basal cup region of naturally infected A. americanum, but not pine tissues that included the endophytic system. Following inoculation of cut shoots, the shoots were abscised from the dwarf mistletoe plant, and the fungus was not isolated 1 year after inoculation. The fungus was recovered from the wounded region of infections that were inoculated with a mycelial plug, but not outside of the wounded area. Hyphae with morphology that matched that of C. gloeosporioides were observed microscopically in the shoots and basal cup region of naturally infected A. americanum, but not in the samples from the inoculated treatments. Thus, we were unable to confirm that C. gloeosporioides infected the endophytic system of A. americanum parasitizing P. contorta var. latifolia, although xylem continuity between the aerial and endophytic systems was observed.
Phase I Clinical and Pharmacokinetic Evaluation of the Vascular-Disrupting Agent OXi4503 in Patients with Advanced Solid Tumors
Authors: Patterson Dan M. , Zweifel Martin , Middleton Mark R. , Price Patricia M. , Folkes Lisa K. , Stratford Michael R.L. , Ross Phil , Halford Sarah , Peters Jane , Balkissoon Jai , Chaplin Dai J. , Padhani Anwar R. , Rustin Gordon J.S. 
Published: January 2012

Abstract
Purpose: Preclinical studies show that OXi4503 (combretastatin A1 diphosphate, CA1P) is more potent than other clinically evaluated vascular-disrupting agents.
Experimental Design: Escalating doses of OXi4503 were given intravenously over 10 minutes on days 1, 8, and 15 every 28 days to patients with advanced solid tumors.
Results: Doses were escalated in single-patient cohorts from 0.06 to 1.92 mg/m2, then expanded cohorts to 15.4 mg/m2 in 43 patients. Common adverse drug reactions were hypertension, tumor pain, anemia, lymphopenia, and easily controllable nausea/vomiting and fatigue. Five patients experienced different drug-related dose-limiting toxicities, atrial fibrillation, increased troponin, blurred vision, diplopia, and tumor lysis. Prophylactic amlodipine failed to prevent adverse events. Pharmacokinetics showed dose-dependent linear increases in peak plasma concentrations and area under the curve value of OXi4503. One partial response was seen in a heavily pretreated patient with ovarian cancer. Dynamic contrast-enhanced MRI confirmed a dose effect and showed significant antivascular effects in 10 of 13 patients treated at doses of 11 mg/m2 or higher.
Conclusions: The maximum tolerated dose was 8.5 mg/m2 but escalation to 14 mg/m2 was possible with only temporary reversible cerebrovascular toxicity by excluding hypertensive patients. As a tumor response was seen at 14 mg/m2 and maximum tumor perfusion reductions were seen at doses of 11 mg/m2 or higher, the recommended phase II dose is from 11 to 14 mg/m2. Clin Cancer Res; 18(5); 1415–25. ©2012 AACR.
Gene Expression, Molecular Class Changes, and Pathway Analysis after Neoadjuvant Systemic Therapy for Breast Cancer
Authors: Gonzalez-Angulo Ana M. , Iwamoto Takayuki , Liu Shuying , Chen Huiqin , Do Kim-Anh , Hortobagyi Gabriel N. , Mills Gordon B. , Meric-Bernstam Funda , Symmans W. Fraser , Pusztai Lajos 
Published: January 2012

Abstract
Purpose: To examine gene expression differences between pre- and post-neoadjuvant systemic therapy (NST) specimens of breast cancers and identify biologic changers that may lead to new therapeutic insights.
Methods: Gene expression data from prechemotherapy fine needle aspiration specimens were compared with resected residual cancers in 21 patients after 4 to 6 months of NST. We removed stroma-associated genes to minimize confounding effects. PAM50 was used to assign molecular class. Paired t test and gene set analysis were used to identify differentially expressed genes and pathways.
Results: The ER and HER2 status based on mRNA expression remained stable in all but two cases, and there were no changes in proliferation metrics (Ki67 and proliferating cell nuclear antigen expression). Molecular class changed in 8 cases (33.3%), usually to normal-like class, which was associated with low residual cancer cell cellularity. The expression of 200 to 600 probe sets changed between baseline and post-NST samples. In basal-like cancers, pathways driven by increased expression of phosphoinositide 3-kinase, small G proteins, and calmodulin-dependent protein kinase II and energy metabolism were enriched, whereas immune cell–derived and the sonic hedgehog pathways were depleted in residual cancer. In non–basal-like breast cancers, notch signaling and energy metabolism (e.g., fatty acid synthesis) were enriched and sonic hedgehog signaling and immune-related pathways were depleted in residual cancer. There was no increase in epithelial–mesenchymal transition or cancer stem cell signatures.
Conclusions: Our data indicate that energy metabolism related processes are upregulated and immune-related signals are depleted in residual cancers. Targeting these biologic processes may represent promising adjuvant treatment strategies for patients with residual cancer. Clin Cancer Res; 18(4); 1109–19. ©2012 AACR.
Mechanisms of Resistance to Crizotinib in Patients with ALK Gene Rearranged Non–Small Cell Lung Cancer
Authors: Doebele Robert C. , Pilling Amanda B. , Aisner Dara L. , Kutateladze Tatiana G. , Le Anh T. , Weickhardt Andrew J. , Kondo Kimi L. , Linderman Derek J. , Heasley Lynn E. , Franklin Wilbur A. , Varella-Garcia Marileila , Camidge D. Ross 
Published: January 2012

Abstract
Purpose: Patients with anaplastic lymphoma kinase (ALK) gene rearrangements often manifest dramatic responses to crizotinib, a small-molecule ALK inhibitor. Unfortunately, not every patient responds and acquired drug resistance inevitably develops in those who do respond. This study aimed to define molecular mechanisms of resistance to crizotinib in patients with ALK+ non–small cell lung cancer (NSCLC).
Experimental Design: We analyzed tissue obtained from 14 patients with ALK+ NSCLC showing evidence of radiologic progression while on crizotinib to define mechanisms of intrinsic and acquired resistance to crizotinib.
Results: Eleven patients had material evaluable for molecular analysis. Four patients (36%) developed secondary mutations in the tyrosine kinase domain of ALK. A novel mutation in the ALK domain, encoding a G1269A amino acid substitution that confers resistance to crizotinib in vitro, was identified in two of these cases. Two patients, one with a resistance mutation, exhibited new onset ALK copy number gain (CNG). One patient showed outgrowth of epidermal growth factor receptor (EGFR) mutant NSCLC without evidence of a persistent ALK gene rearrangement. Two patients exhibited a KRAS mutation, one of which occurred without evidence of a persisting ALK gene rearrangement. One patient showed the emergence of an ALK gene fusion–negative tumor compared with the baseline sample but with no identifiable alternate driver. Two patients retained ALK positivity with no identifiable resistance mechanism.
Conclusions: Crizotinib resistance in ALK+ NSCLC occurs through somatic kinase domain mutations, ALK gene fusion CNG, and emergence of separate oncogenic drivers. Clin Cancer Res; 18(5); 1472–82. ©2012 AACR.
Contemporary use of glycoprotein IIb/IIIa inhibitors
Authors: Würtz Morten , Grove Erik , Caterina Raffaele , Huber Kurt , Moliterno David , Neumann Franz-Josef , Kristensen Steen 
Published: January 2012

SummaryPlatelet glycoprotein IIb/IIIa inhibitors (GPI) are antithrombotic agents preventing the binding of fibrinogen to GP IIb/IIIa receptors. Thus, GPI interfere with interplatelet bridging mediated by fibrinogen. Currently, three generic GPI with different antithrombotic properties are available for intravenous administration: abciximab, eptifibatide, and tirofiban. The development of oral GPI was abandoned, whereas intravenous GPI were introduced in various clinical settings during the 1990s, yielding substantial benefit in the treatment of acute coronary syndromes, particularly during percutaneous coronary interventions. Results of the many randomised trials evidenced the efficacy of this drug class, though these trials were conducted prior to the emergence of modern oral antiplatelet therapy with efficient P2Y12 inhibitors. Subsequent trials failed to consolidate the strongly favourable impression of GPI, and indications for their use have been more restricted in recent years. Nonetheless, GPI may still be beneficial during coronary interventions among high-risk patients including acute ST-elevation and non-ST-elevation myocardial infarctions, particularly in the absence of adequate pretreatment with oral antiplatelet drugs or when direct thrombin inhibitors are not utilised. Intracoronary GPI administration has been suggested as adjunctive therapy during primary percutaneous coronary intervention, and the results of larger ongoing trials are expected to elucidate its clinical potential. The present review outlines the key milestones of GPI development and provides an up-to-date overview of the clinical applicability of these drugs in the era of refined coronary stenting, potent antithrombotic drugs, and novel thrombin inhibiting agents.
Regulatory regions of SERPINC1 gene: Identification of the first mutation associated with antithrombin deficiency
Authors: de la Morena-Barrio María , Antón Ana , Martínez-Martínez Irene , Padilla José , Miñano Antonia , Navarro-Fernández José , Águila Sonia , López María , Fontcuberta Jordi , Vicente Vicente , Corral Javier 
Published: January 2012

SummaryAntithrombin is the main endogenous anticoagulant. Impaired function or deficiency of this molecule significantly increases the risk of thrombosis. We studied the genetic variability of SERPINC1, the gene encoding antithrombin, to identify mutations affecting regulatory regions with functional effect on its levels. We sequenced 15,375 bp of this gene, including the potential promoter region, in three groups of subjects: five healthy subjects with antithrombin levels in the lowest (75%) and highest (115%) ranges of our population, 14 patients with venous thrombosis and a moderate antithrombin deficiency as the single thrombophilic defect, and two families with type I antithrombin deficiency who had neither mutations affecting exons or flanking regions, nor gross gene deletions. Our study confirmed the low genetic variability of SERPINC1, particularly in the coding region, and its minor influence in the heterogeneity of antithrombin levels. Interestingly, in one family, we identified a g.2143 C>G transversion, located 170 bp upstream from the translation initiation codon. This mutation affected one of the four regions located in the minimal promoter that have potential regulatory activity according to previous DNase footprinting protection assays. Genotype-phenotype analysis in the affected family and reporter analysis in different hepatic cell lines demonstrated that this mutation significantly impaired, although it did not abolish, the downstream transcription. Therefore, this is the first mutation affecting a regulatory region of the SERPINC1 gene associated with antithrombin deficiency. Our results strongly sustain the inclusion of the promoter region of SERPINC1 in the molecular analysis of patients with antithrombin deficiency.
Medicare Services Provided by Cardiologists in the United States: 1999–2008
Authors: Andrus Bruce W. , Welch H. Gilbert 
Published: January 2012

Background—
Services provided by cardiologists represent a major portion of Medicare expenditures for specialist physicians. The absolute growth and distribution of these services over the past decade have not been well described.

Methods and Results—
We analyzed fee-for-service Medicare Part B claims for each year from 1999–2008 and selected claims from physicians whose specialty code was cardiology. We then grouped approximately 1000 CPT-9 codes into 45 specific service groups that were then further aggregated into 3 broad service categories: evaluation and management, noninvasive procedures, and invasive procedures. Our main outcome measures were services and allowed charges per 1000 beneficiaries. Sample size ranged from 30.9 million beneficiaries in 1999 to 31.7 million in 2008. During this 10-year period, the number of claims from cardiologists increased 44% (from 2082–2997 per 1000 beneficiaries) while the allowed charges increased 28% after adjusting for inflation (in 2008 dollars, from $181 397–231 728 per 1000 beneficiaries). Evaluation and management services and invasive procedures contributed relatively little to this growth. Instead, most of the growth involved noninvasive procedures—with a 70% increase in claims. Although the most dramatic increases in noninvasive procedures involved emerging imaging technologies (cardiac CT, MRI, and PET scanning), the bulk of the growth occurred in two established technologies: resting echocardiograms and stress tests with nuclear imaging.

Conclusions—
Most of the growth in services provided by cardiologists over the past decade is the result of increased noninvasive imaging.
Assessment of Nutritional Status Using Anthropometric Methods on 1–4 Year Old Children in an Urban Ghetto in Lagos, Nigeria
Authors: Abidoye R.O. , Ihebuzor N.N. 
Published: January 2012

This study assessed the nutritional status using anthropometry of 1–4 year old children in an urban slum in the Mushin Local Government Area of Lagos State, with a view to determining the impact of urbanization on child health. A total of 365 children were enrolled using multistage random sampling techniques. Anthropometric measurements used were weight and height. Height-for-age, weight-for-height, and weight-for-age Z-scores below −2.00 SD of the reference NCHS standard were used to define stunting, wasting and underweight, respectively. The study revealed a prevalence of underweight of 39.2%, stunting of 34.5% and wasting of 21.9%. The mean of weight-for-age, height-for-age, weight-for-height and mid-upper-arm-circumference were less than the mean of the NCHS reference population. This difference might be due to the socio economic back grounds of the two populations. Using the modified Wellcome Classification of malnutrition, 37.8% of the children were malnourished. Most subjects came from homes with inadequate water supply and poor refuse disposal methods.
Anthropometric Measurements of Infants and Under Five Children in Riyadh City
Authors: Al-Jassir Mohammed Saleh , El Bashir Bushra 
Published: January 2012

The data presented in this paper are part of the ongoing pediatric nutrition surveillance in ten primary health centers from Riyadh City. A total of 21,507 infants and children under five were included. The mean birth weight was 3027g, and 8.6% of the children had low birth weights. The measurements showed that there had been no obvious change in the weights and heights of children during the past 13 years. In our results the children classified as moderate and severely underweight were 4.5% and 0.8% respectively. The data showed the average growth of all infants, regardless of feeding pattern, was same or faster than the NCHS reference population, up to approximately six months of age after which their growth became slower than that of the NCHS standards. The prevalence of malnutrition in Saudi Arabia is moderately high, in spite of the high per capita income, and the fact that the government subsidizes locally produced and imported food items. The malnutrition among this age group may be attributed to reproductive or social behavior and genetic factors. The reduction of malnutrition in the last ten years could be largely due to the nutrition and health education programs. There is a need for more comprehensive nutritional health education among the local population.
Nutritional Quality of Meals in Nursing Homes and Meals on Wheels for Elderly Persons in Croatia
Authors: Colić Barić Irena , Šatalić Zvonimir , Keser Irena 
Published: January 2012

The aim of the study was to evaluate the adequacy of meals provided for elderly residents and non-residents of nursing homes in Croatia. Menus of 44 all-day meals provided for residents from 4 nursing homes and 34 meals on wheels provided for non-residents of low socioeconomic status were selected by random sampling. A questionnaire was used to determine socioeconomic status and attitude of residents (n = 89) and non-residents (n = 80) regarding meals offered. An average energy value of all-day meals and meals on wheels was 96.7 and 39.8% RDA respectively. All-day meals provide adequate amounts of the micronutrients examined (phosphorus, iron, thiamine, riboflavin, niacin and vitamin C) with exception of calcium. Fat provided 35% and 36% of energy for all-day meals and meals on wheels respectively. The body mass index (BMI) under 18.5 kg/m2 had 1.7% residents and 4.0% non-residents. BMI higher than 24.9 kg/m2 were observed in 50% and 47% of residents and non-residents respectively. Gender differences were observed for meal preferences offered to both residents and non-residents. The meals provided adequate amounts of energy and the micronutrients examined. However, a decrease in the energy fraction of fat and decrease in protein content would be advisable.
Scientific or Social Priorities for Brain Science? – Making a Difference
Authors: Ashcroft Richard E. 
Published: January 2012

How we ought to prioritise research spending is a difficult problem. On the one hand, we may wish to target research resources on the problems of most pressing social need, but this may be to pose questions which science is not in a position to answer. On the other hand, we may wish to target research resources on the problems which are for scientific reasons most interesting or most tractable, accepting that this might not be to target the most pressing social needs. Current thinking is that research priorities can be set most fairly not by specifying principles of justice in research spending, but rather by making the decision-making process more open, transparent and perhaps democratic. This can involve patient or citizen involvement in research programme design or research funding decision-making.