bluuebunny/crossref_metadata_2025 huggingface dataset:
A Healthy Bottom Line
Authors: Ken Ivy
Published: March 2014

Corporations rarely prioritize healthy communities over healthy profit margins, but their profits depend on community acceptance. This article reveals that in their quest to be perceived as legitimate citizens, some corporations co-opt the rhetorical tactics typically associated with social movement organizations to frame their profit-maximizing practices as the solution to the problem of childhood obesity. In this framing, explored here in an ethnography of the activities of two organizations called the Partnership for a Healthier America and the Alliance for a Healthier Generation, obesity is the result of communities’ failure to work together and the cumulative effect of individuals’ bad choices. By framing corporations as vital community partners poised to “work together” across sectors to solve the childhood obesity “crisis,” these organizations hope to inspire the public to participate in this imagined community in one predominant way: by buying their products. Despite the apparent power and reach of their framing, though, these corporations implicitly acknowledge that they are not and cannot be legitimate members of communities unless the public lets them.
Causative organisms of post-traumatic endophthalmitis: a 20-year retrospective study
Authors: Long Chongde , Liu Bingqian , Xu Chaochao , Jing Yuan , Yuan Zhaohui , Lin Xiaofeng
Published: March 2014

Background

A wide range of organisms that enter the eye following ocular trauma can cause endophthalmitis. This study was to investigate the spectrum of pathogens and antibiotic susceptibility of bacterial isolates from a large cohort of post-traumatic endophthalmitis cases.

Methods

A retrospective study of 912 post-traumatic endophthalmitis patients treated at a tertiary eye-care center in China was performed. The associations between risk factors and the most common isolated organisms were investigated by Chi square Test. The percent susceptibilities for the first 10 years (1990–1999) and the second 10 years (2000–2009) were compared by Chi square test. p < 0.05 was considered statistically significant.

Results

Three-hundred-forty-seven (38.1%) cases of endophthalmitis were culture-positive, and 11 (3.2%) showed mixed infections (Gram-negative bacilli and fungi), yielding a total of 358 microbial pathogens. Culture proven organisms included 150 (41.9%) Gram-positive cocci, 104 (29.1%) Gram-negative bacilli, 44 (12.3%) Gram-positive bacilli, and 60 (16.8%) fungi. The coagulase-negative staphylococcal (CNS) species S. epidermidis (21.8%) and S. saprophyticus (12.0%) were the predominant pathogens, followed by Bacillus subtilis (8.7%), Pseudomonas aeruginosa (7.8%), and Escherichia coli (6.4%). Delayed repair over 24 h (p < 0.001) and metallic injury (p < 0.01) were significantly associated with positive culture of CNS. The most frequent fungal species were Aspergillus (26/60), followed by yeast-like fungi (18/60). P. aeruginosa was relatively sensitive to ciprofloxacin (83.3%), cefoperazone (75%), tobramycin (75%), cefuroxime (75%), and ceftazidime (75%) during the second decade. Multi-drug resistance was observed in the predominant Gram-negative bacteria.

Conclusion

We identified a broad spectrum of microbes causing post-traumatic endophthalmitis, with Gram-positive cocci the most frequently identified causative organism, followed by Bacillus species, fungi, and mixed infections. CNS infection was statistically associated with delayed repair and metallic injury. Variation in antibiotic susceptibility was observed among isolated bacteria and between different periods. Ciprofloxacin and ceftazidime in the first and second decades of the study, respectively, showed the highest activity against bacterial post-traumatic endophthalmitis. For infections caused by P. aeruginosa, a combination therapy of ciprofloxacin, tobramycin, and one of the cephalosporins might provide optimal coverage according to data from the second decade.
Simple and reusable picoinjector for liquid delivery via nanofluidics approach
Authors: Li Shunbo , Cao Wenbin , Hui Yu Sanna , Wen Weijia
Published: March 2014

Precise control of sample volume is one of the most important functions in lab-on-a-chip (LOC) systems, especially for chemical and biological reactions. The common approach used for liquid delivery involves the employment of capillaries and microstructures for generating a droplet which has a volume in the nanoliter or picoliter range. Here, we report a novel approach for constructing a picoinjector which is based on well-controlled electroosmotic (EO) flow to electrokinetically drive sample solutions. This picoinjector comprises an array of interconnected nanochannels for liquid delivery. Such technique for liquid delivery has the advantages of well-controlled sample volume and reusable nanofluidic chip, and it was reported for the first time. In the study of the pumping process for this picoinjector, the EO flow rate was determined by the intensity of the fluorescent probe. The influence of ion concentration in electrolyte solutions over the EO flow rate was also investigated and discussed. The application of this EO-driven picoinjector for chemical reactions was demonstrated by the reaction between Fluo-4 and calcium chloride with the reaction cycle controlled by the applied square waves of different duty cycles. The precision of our device can reach down to picoliter per second, which is much smaller than that of most existing technologies. This new approach, thus, opens further possibilities of adopting nanofluidics for well-controlled chemical reactions with particular applications in nanoparticle synthesis, bimolecular synthesis, drug delivery, and diagnostic testing.

PACS

85.85.+ j; 87.15.hj; 82.39.Wj
The Effect of Acupuncture Needle Combination on Central Pain Processing-An fMRI Study
Authors: Leung Albert , Zhao Yi , Shukla Shivshil
Published: March 2014

Background:

Empirical acupuncture treatment paradigm for acute pain utilizing Tendinomuscular Meridians (TMM) calls for the stimulation of Ting Points (TPs) and Gathering point(GP). This study aims to compare the supraspinal neuronal mechanisms associated with both TPs and GP needling (EA3), and TPs needling alone (EA2) with fMRI.

Results:

A significant (P < 0.01) difference between pre-scan (heat Pain) HP, and post-EA HP VAS scores in both paradigms was noted (n = 11). The post-EA HP VAS score was significantly (P < 0.05) lower with EA3 comparing to EA2 Within-group random effect analysis indicated that EA3+HP>EA3 (condition EA3+HP subtracted by condition EA3) appeared to exert a significant degree of activity suppression in the affective supraspinal regions including the IPL, anterior cingulate cortex (ACC) and the insular cortex (IN). This level of suppression was not observed in the EA2+HP>EA2 (condition EA2+HP subtracted by condition EA2) within-group random effect analysis Between-group random effect analysis indicated that EA3 induced a significantly (P < 0.01, cluster size threshold 150) higher degree of deactivation than EA2 in several pain related supraspinal regions including the right prefrontal cortex, rostral anterior cingulate (rACC), medial cingulate cortex, left inferior frontal lobe and posterior cerebellum. The 2-factor ANOVA in those regions indicated both rACC and posterior cerebellum had a significant (P < 0.01) needle effect, and the right prefrontal area showed a significant (P < 0.01) HP effect. However, a significant interaction between the two factors was only found in the right prefrontal lobe. Granger causality analysis showed EA3 induced a much higher degree of inference among HP related supraspinal somatosensory, affective and modulatory components than EA2. Deactivation pattern at the medullary-pontine area casted a direct inference on the deactivation pattern of secondary somatosensory cortices which also affected the deactivation of the IN.

Conclusions:

While both EA2 and EA3 induced a significant degree of deactivation in the human brain regions related to pain processing, the addition of GP stimulation further exerts an inhibitory effect on the ascending spinoreticular pain pathway. Therefore, different needling position as mandated in different empirical acupuncture treatment paradigms may play a different role in modulating pain related neuronal functions.
Treatment preferences amongst physical therapists and chiropractors for the management of neck pain: results of an international survey
Authors: Carlesso Lisa C , MacDermid Joy C , Gross Anita R , Walton David M , Santaguida P Lina
Published: March 2014

Background

Clinical practice guidelines on the management of neck pain make recommendations to help practitioners optimize patient care. By examining the practice patterns of practitioners, adherence to CPGs or lack thereof, is demonstrated. Understanding utilization of various treatments by practitioners and comparing these patterns to that of recommended guidelines is important to identify gaps for knowledge translation and improve treatment regimens.

Aim

To describe the utilization of interventions in patients with neck pain by clinicians.

Methods

A cross-sectional international survey was conducted from February 2012 to March 2013 to determine physical medicine, complementary and alternative medicine utilization amongst 360 clinicians treating patients with neck pain.

Results

The survey was international (19 countries) with Canada having the largest response (38%). Results were analyzed by usage amongst physical therapists (38%) and chiropractors (31%) as they were the predominant respondents. Within these professions, respondents were male (41-66%) working in private practice (69-95%). Exercise and manual therapies were consistently (98-99%) used by both professions but tests of subgroup differences determined that physical therapists used exercise, orthoses and ‘other’ interventions more, while chiropractors used phototherapeutics more. However, phototherapeutics (65%), Orthoses/supportive devices (57%), mechanical traction (55%) and sonic therapies (54%) were not used by the majority of respondents. Thermal applications (73%) and acupuncture (46%) were the modalities used most commonly. Analysis of differences across the subtypes of neck pain indicated that respondents utilize treatments more often for chronic neck pain and whiplash conditions, followed by radiculopathy, acute neck pain and whiplash conditions, and facet joint dysfunction by diagnostic block. The higher rates of usage of some interventions were consistent with supporting evidence (e.g. manual therapy). However, there was moderate usage of a number of interventions that have limited support or conflicting evidence (e.g. ergonomics).

Conclusions

This survey indicates that exercise and manual therapy are core treatments provided by chiropractors and physical therapists. Future research should address gaps in evidence associated with variable practice patterns and knowledge translation to reduce usage of some interventions that have been shown to be ineffective.
Immigrant influx and social cohesion erosion
Authors: Neymotin Florence
Published: March 2014

If immigration causes a decrease in social cohesion, then it may also be an important contributing factor in the recent failure of financial institutions. The present analysis finds some evidence for a negative relationship between immigration and volunteering from the Current Population Survey 2004–2008 September Supplements. Various specifications confirm the tendency of immigrant inflows to decrease social cohesion, as measured by the tendency of native U.S. citizens to volunteer. Differences in effect by type of volunteering organization, country of origin of immigrants, functional form, and voting as the relevant measure of social cohesion are explored with similar patterns of results. Differences in effect by city size provide a counterpoint, lending support to the alternative idea that immigration does not in fact decrease social cohesion.

JEL codes

H8; Z13; J61
Predictors of physical restraint use in Canadian intensive care units
Authors: Luk Elena , Sneyers Barbara , Rose Louise , Perreault Marc M , Williamson David R , Mehta Sangeeta , Cook Deborah J , Lapinsky Stephanie C , Burry Lisa
Published: March 2014

Introduction

Physical restraint (PR) use in the intensive care unit (ICU) has been associated with higher rates of self-extubation and prolonged ICU length of stay. Our objectives were to describe patterns and predictors of PR use.

Methods

We conducted a secondary analysis of a prospective observational study of analgosedation, antipsychotic, neuromuscular blocker, and PR practices in 51 Canadian ICUs. Data were collected prospectively for all mechanically ventilated adults admitted during a two-week period. We tested for patient, treatment, and hospital characteristics that were associated with PR use and number of days of use, using logistic and Poisson regression respectively.

Results

PR was used on 374 out of 711 (53%) patients, for a mean number of 4.1 (standard deviation (SD) 4.0) days. Treatment characteristics associated with PR were higher daily benzodiazepine dose (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.00 to 1.11), higher daily opioid dose (OR 1.04, 95% CI 1.01 to 1.06), antipsychotic drugs (OR 3.09, 95% CI 1.74 to 5.48), agitation (Sedation-Agitation Scale (SAS) >4) (OR 3.73, 95% CI 1.50 to 9.29), and sedation administration method (continuous and bolus versus bolus only) (OR 3.09, 95% CI 1.74 to 5.48). Hospital characteristics associated with PR indicated patients were less likely to be restrained in ICUs from university-affiliated hospitals (OR 0.32, 95% CI 0.17 to 0.61). Mainly treatment characteristics were associated with more days of PR, including: higher daily benzodiazepine dose (incidence rate ratio (IRR) 1.07, 95% CI 1.01 to 1.13), daily sedation interruption (IRR 3.44, 95% CI 1.48 to 8.10), antipsychotic drugs (IRR 15.67, 95% CI 6.62 to 37.12), SAS <3 (IRR 2.62, 95% CI 1.08 to 6.35), and any adverse event including accidental device removal (IRR 8.27, 95% CI 2.07 to 33.08). Patient characteristics (age, gender, Acute Physiology and Chronic Health Evaluation II score, admission category, prior substance abuse, prior psychotropic medication, pre-existing psychiatric condition or dementia) were not associated with PR use or number of days used.

Conclusions

PR was used in half of the patients in these 51 ICUs. Treatment characteristics predominantly predicted PR use, as opposed to patient or hospital/ICU characteristics. Use of sedative, analgesic, and antipsychotic drugs, agitation, heavy sedation, and occurrence of an adverse event predicted PR use or number of days used.
Vitamin D status and its association with season, hospital and sepsis mortality in critical illness
Authors: Amrein Karin , Zajic Paul , Schnedl Christian , Waltensdorfer Andreas , Fruhwald Sonja , Holl Alexander , Purkart Tadeja Urbanic , Wünsch Gerit , Valentin Thomas , Grisold Andrea , Stojakovic Tatjana , Amrein Steven , Pieber Thomas R , Dobnig Harald
Published: March 2014

Introduction

Vitamin D plays a key role in immune function. Deficiency may aggravate the incidence and outcome of infectious complications in critically ill patients. We aimed to evaluate the prevalence of vitamin D deficiency and the correlation between serum 25-hydroxyvitamin D (25(OH) D) and hospital mortality, sepsis mortality and blood culture positivity.

Methods

In a single-center retrospective observational study at a tertiary care center in Graz, Austria, 655 surgical and nonsurgical critically ill patients with available 25(OH) D levels hospitalized between September 2008 and May 2010 were included. Cox regression analysis adjusted for age, gender, severity of illness, renal function and inflammatory status was performed. Vitamin D levels were categorized by month-specific tertiles (high, intermediate, low) to reflect seasonal variation of serum 25(OH) D levels.

Results

Overall, the majority of patients were vitamin D deficient (<20 ng/ml; 60.2%) or insufficient (≥20 and <30 ng/dl; 26.3%), with normal 25(OH) D levels (>30 ng/ml) present in only 13.6%. The prevalence of vitamin D deficiency and mean 25(OH) D levels was significantly different in winter compared to summer months (P <0.001). Hospital mortality was 20.6% (135 of 655 patients). Adjusted hospital mortality was significantly higher in patients in the low (hazard ratio (HR) 2.05, 95% confidence interval (CI) 1.31 to 3.22) and intermediate (HR 1.92, 95% CI 1.21 to 3.06) compared to the high tertile. Sepsis was identified as cause of death in 20 of 135 deceased patients (14.8%). There was no significant association between 25(OH) D and C-reactive protein (CRP), leukocyte count or procalcitonin levels. In a subgroup analysis (n = 244), blood culture positivity rates did not differ between tertiles (23.1% versus 28.2% versus 17.1%, P = 0.361).

Conclusions

Low 25(OH) D status is significantly associated with mortality in the critically ill. Intervention studies are needed to investigate the effect of vitamin D substitution on mortality and sepsis rates in this population.
When more is better
Authors: Pichard Claude
Published: March 2014

Nutrition support of critically ill patients with sepsis is one of the most debated issues among intensivists. The latest international sepsis guidelines recommend the prescription of a low volume of feeds through gastric or intestinal enteral nutrition (EN) for 7 days after admission to the ICU. The data to support such recommendations are scarce, and large trials are needed to clarify this issue. As reported in the previous issue of Critical Care, Elke and colleagues have revisited a database containing 13,630 ICU patients, of whom 2,270 met four inclusion criteria: sepsis or pneumonia, ICU stay of at least 3 days, mechanical ventilation within 48 hours after ICU admission, and exclusive EN. The goal of the authors was to assess the impact of various levels of energy and protein administration on mortality at 60 days after ICU admission and on the duration of mechanical ventilation. They found that standard levels of energy and protein recommended by international guidelines for patients in the ICU do also apply to patients with sepsis in the ICU. This is an important finding, which contradicts the current recommendations and beliefs for this subgroup of patients in the ICU and gives a strong rationale for launching a large prospective randomized trial.
The consequences of sudden fluid shifts on body composition in critically ill patients
Authors: Ismael Sophie , Savalle Magali , Trivin Claire , Gillaizeau Florence , D’Auzac Christian , Faisy Christophe
Published: March 2014

Introduction

Estimation of body composition as fat-free mass (FFM) is subjected to many variations caused by injury and stress conditions in the intensive care unit (ICU). Body cell mass (BCM), the metabolically active part of FFM, is reported to be more specifically correlated to changes in nutritional status. Bedside estimation of BCM could help to provide more valuable markers of nutritional status and may promote understanding of metabolic consequences of energy deficit in the ICU patients. We aimed to quantify BCM, water compartments and FFM by methods usable at the bedside for evaluating the impact of sudden and massive fluid shifts on body composition in ICU patients.

Methods

We conducted a prospective experimental study over an 6 month-period in a 18-bed ICU. Body composition of 31 consecutive hemodynamically stable patients requiring acute renal replacement therapy for fluid overload (ultrafiltration ≥5% body weight) was investigated before and after the hemodialysis session. Intra-(ICW) and extracellular (ECW) water volumes were calculated from the raw values of the low- and high-frequency resistances measured by multi-frequency bioelectrical impedance. BCM was assessed by a calculated method recently developed for ICU patients. FFM was derived from BCM and ECW.

Results

Intradialytic weight loss was 3.8 ± 0.8 kg. Percentage changes of ECW (-7.99 ± 4.60%) and of ICW (-7.63 ± 5.11%) were similar, resulting ECW/ICW ratio constant (1.26 ± 0.20). The fall of FFM (-2.24 ± 1.56 kg, -4.43 ± 2.65%) was less pronounced than the decrease of ECW (P < 0.001) or ICW (P < 0.001). Intradialytic variation of BCM was clinically negligible (-0.38 ± 0.93 kg, -1.56 ± 3.94%) and was significantly less than FFM (P < 0.001).

Conclusions

BCM estimation is less driven by sudden massive fluid shifts than FMM. Assessment of BCM should be preferred to FFM when severe hydration disturbances are present in ICU patients.
Optimal cerebral perfusion pressure in patients with intracerebral hemorrhage: an observational case series
Authors: Diedler Jennifer , Santos Edgar , Poli Sven , Sykora Marek
Published: March 2014

Introduction

Current guidelines for spontaneous intracerebral hemorrhage (ICH) recommend maintaining cerebral perfusion pressure (CPP) between 50 and 70 mmHg, depending on the state of autoregulation. We continuously assessed dynamic cerebral autoregulation and the possibility of determination of an optimal CPP (CPPopt) in ICH patients. Associations between autoregulation, CPPopt and functional outcome were explored.

Methods

Intracranial pressure (ICP), mean arterial pressure (MAP) and CPP were continuously recorded in 55 patients, with 38 patients included in the analysis. The pressure reactivity index (PRx) was calculated as moving correlation between MAP and ICP. CPPopt was defined as the CPP associated with the lowest PRx values. CPPopt was calculated using hourly updated of 4 hour windows. The modified Rankin Scale (mRS) was assessed at 3 months and associations between PRx, CPPopt and outcomes were explored using Pearson correlation and Fisher’s exact test. Multivariate stepwise logistic regression models were calculated including standard outcome predictors along with percentage of time with PRx >0.2 and percentage of time within the CPPopt range.

Results

An overall PRx indicating impairment of pressure reactivity was found in 47% of patients (n = 18). The mean PRx and the time spent with a PRx > 0.2 significantly correlated with mRS at 3 months (r = 0.50, P = 0.002; r = 0.46, P = 0.004). CPPopt was calculable during 57% of the monitoring time. The median CPP was 78 mmHg, the median CPPopt 83 mmHg. Mortality was lowest in the group of patients with a CPP close to their CPPopt. However, for none of the CPPopt variables a significant association to outcome was found. The percentage of time with impaired autoregulation and hemorrhage volume were independent predictors for acceptable outcome (mRS 1 to 4) at three months.

Conclusions

Failure of pressure reactivity seems common following severe ICH and is associated with unfavorable outcome. Real-time assessment of CPPopt is feasible in ICH and might provide a tool for an autoregulation-oriented CPP management. A larger trial is needed to explore if a CPPopt management results in better functional outcomes.
Correcting for cell-type composition bias in epigenome-wide association studies
Authors: Lowe Robert , Rakyan Vardhman K
Published: March 2014

Recent epigenome-wide association studies have indicated a potential role for epigenetic variation in the etiology of complex human diseases. However, one major challenge is to distinguish true epigenetic variation from changes caused by differences in cellular composition between the disease and non-disease state, a problem that is particularly relevant when analyzing whole blood. For studies with large numbers of samples, it can be expensive and very time consuming to perform cell sorting, and it is often not clear which is the correct cell type to profile. Two recently published papers have attempted to address this confounding issue using bioinformatics.
Metastatic Neuroblastoma Confined to Distant Lymph Nodes (stage 4N) Predicts Outcome in Patients With Stage 4 Disease: A Study From the International Neuroblastoma Risk Group Database
Authors: Morgenstern Daniel A. , London Wendy B. , Stephens Derek , Volchenboum Samuel L. , Hero Barbara , Di Cataldo Andrea , Nakagawara Akira , Shimada Hiroyuki , Ambros Peter F. , Matthay Katherine K. , Cohn Susan L. , Pearson Andrew D.J. , Irwin Meredith S.
Published: March 2014

Purpose

The presence of distant metastases is one of the most powerful predictors of outcome in patients with neuroblastoma. However, the pattern of metastatic spread is not incorporated into current risk stratification systems. Small case series have suggested that patients with neuroblastoma who have metastatic disease limited to distant lymph nodes (4N disease) may have improved outcomes.

Patients and Methods

We analyzed retrospective data from the International Neuroblastoma Risk Group database for patients diagnosed from 1990 to 2002. 4N patients were compared with the remaining stage 4 patients (non-4N), excluding those with missing metastatic site data.

Results

In all, 2,250 International Neuroblastoma Staging System stage 4 patients with complete data were identified, of whom 146 (6.5%) had 4N disease. For 4N patients, event-free survival (EFS; 5-year, 77% ± 4%) and overall survival (OS; 5-year, 85% ± 3%) were significantly better than EFS (5-year, 35% ± 1%) and OS (5-year, 42% ± 1%) for non-4N stage 4 patients (P < .001). 4N patients were more likely to be younger (P < .001) and have tumors with favorable characteristics, including absence of MYCN amplification (89% v 69%; P < .001). In a multivariable analysis, 4N disease remained a significant predictor of outcome (hazard ratio for non-4N v 4N: 3.40 for EFS and 3.69 for OS). Within subgroups defined by age at diagnosis and tumor MYCN status, 4N disease was significantly associated with improved outcomes.

Conclusion

4N represents a subgroup with better outcome than that of other patients with metastatic disease. These findings suggest that the biology and treatment response of 4N tumors differ from other stage 4 tumors, and less intensive therapy should be considered for this cohort. Future exploration of biologic factors determining the pattern of metastatic spread is warranted.
Stand Up to Cancer Phase Ib Study of Pan-Phosphoinositide-3-Kinase Inhibitor Buparlisib With Letrozole in Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer
Authors: Mayer Ingrid A. , Abramson Vandana G. , Isakoff Steven J. , Forero Andres , Balko Justin M. , Kuba María Gabriela , Sanders Melinda E. , Yap Jeffrey T. , Van den Abbeele Annick D. , Li Yisheng , Cantley Lewis C. , Winer Eric , Arteaga Carlos L.
Published: March 2014

Purpose

Buparlisib, an oral reversible inhibitor of all class I phosphoinositide-3-kinases, has shown antitumoral activity against estrogen receptor (ER)-positive breast cancer cell lines and xenografts, alone and with endocrine therapy. This phase Ib study evaluated buparlisib plus letrozole's safety, tolerability, and preliminary activity in patients with metastatic ER-positive breast cancer refractory to endocrine therapy.

Patients and Methods

Patients received letrozole and buparlisib in two different administration schedules. Outcomes were assessed by standard solid-tumor phase I methods. [18F]fluorodeoxyglucose–positron emission tomography/computed tomography ([18F]FDG-PET/CT) scans were done at baseline and 2 weeks after treatment initiation. Tumor blocks were collected for phosphoinositide-3-kinase pathway mutation analysis.

Results

Fifty-one patients were allocated sequentially to continuous or intermittent (five on/two off days) buparlisib administration on an every-4-week schedule. Buparlisib's maximum-tolerated dose (MTD) was 100 mg/d. Common drug-related adverse events included ≤ grade 2 hyperglycemia, nausea, fatigue, transaminitis, and mood disorders. The clinical benefit rate (lack of progression ≥ 6 months) among all patients treated at the MTD was 31%, including two objective responses in the continuous dose arm. Of seven patients remaining on treatment ≥ 12 months, three had tumors with PIK3CA hot-spot mutation. Patients exhibiting metabolic disease progression by [18F]FDG-PET/CT scan at 2 weeks progressed rapidly on therapy.

Conclusion

The letrozole and buparlisib combination was safe, with reversible toxicities regardless of schedule administration. Clinical activity was observed independent of PIK3CA mutation status. No metabolic response by [18F]FDG-PET/CT scan at 2 weeks was associated with rapid disease progression. Phase III trials of buparlisib and endocrine therapy in patients with ER-positive breast cancer are ongoing.
Fractional Discrete Processes: Compound and Mixed Poisson Representations
Authors: Beghin Luisa , Macci Claudio
Published: March 2014

We consider two fractional versions of a family of nonnegative integer-valued processes. We prove that their probability mass functions solve fractional Kolmogorov forward equations, and we show the overdispersion of these processes. As particular examples in this family, we can define fractional versions of some processes in the literature as the Pólya-Aeppli process, the Poisson inverse Gaussian process, and the negative binomial process. We also define and study some more general fractional versions with two fractional parameters.
Relations Between Hidden Regular Variation and the Tail Order of Copulas
Authors: Hua Lei , Joe Harry , Li Haijun
Published: March 2014

We study the relations between the tail order of copulas and hidden regular variation (HRV) on subcones generated by order statistics. Multivariate regular variation (MRV) and HRV deal with extremal dependence of random vectors with Pareto-like univariate margins. Alternatively, if one uses a copula to model the dependence structure of a random vector then the upper exponent and tail order functions can be used to capture the extremal dependence structure. After defining upper exponent functions on a series of subcones, we establish the relation between the tail order of a copula and the tail indexes for MRV and HRV. We show that upper exponent functions of a copula and intensity measures of MRV/HRV can be represented by each other, and the upper exponent function on subcones can be expressed by a Pickands-type integral representation. Finally, a mixture model is given with the mixing random vector leading to the finite-directional measure in a product-measure representation of HRV intensity measures.
On the Nearest-Neighbor Algorithm for the Mean-Field Traveling Salesman Problem
Authors: Bandyopadhyay Antar , Sajadi Farkhondeh
Published: March 2014

In this work we consider the mean-field traveling salesman problem, where the intercity distances are taken to be independent and identically distributed with some distribution F. We consider the simplest approximation algorithm, namely, the nearest-neighbor algorithm, where the rule is to move to the nearest nonvisited city. We show that the limiting behavior of the total length of the nearest-neighbor tour depends on the scaling properties of the density of F at 0 and derive the limits for all possible cases of general F.
Letter: Characterization of Volatile and Semi-Volatile Compounds in Green and Fermented Leaves of Bergenia Crassifolia L. by Gas Chromatography-Mass Spectrometry and ID-CUBE Direct Analysis in Real Time-High Resolution Mass Spectrometry
Authors: Chernetsova Elena S. , Shikov Alexander N. , Crawford Elizabeth A. , Grashorn Sebastian , Laakso I. , Pozharitskaya Olga N. , Makarov Valery G. , Hiltunen Raimo , Galambosi Bertalan , Morlock Gertrud E.
Published: March 2014

Chemical compositions of volatile and semi-volatile components in green and fermented leaves of Bergenia crassifolia L. were studied. Leaf components were identified using gas chromatography with low resolution mass spectrometry and direct analysis in real time (DART) high resolution mass spectrometry with an ID-CUBE ion source. Phytol, nerolidol, geraniol, linalool, α-bisabolol, α-bisabololoxide B, α-cadinol, δ-cadinene, α-terpineol and several other marker compounds of special interest were defined, for which the process of fermentation significantly changed their content in the leaves. Low resolution EI GC-MS and ID-CUBE DART-HRMS were found to be complementary methods, as they provide different information, helpful to increase the confidence of identification.
Electrospray Ion Mobility Mass Spectrometry of Positively Charged Sodium Bis(2-Ethylhexyl)Sulfosuccinate Aggregates
Authors: Bongiorno David , Indelicato Serena , Giorgi Gianluca , Scarpella Simona , Liveri Vincenzo Turco , Ceraulo Leopoldo
Published: March 2014

Collision cross-sections (CCS) of positively singly and multiply charged aggregates of the surfactant sodium bis(2-ethylhexyl)sulfosuccinate (AOTNa) in the gas phase have been measured by quadrupole ion mobility time-of-flight mass spectrometry. Calibration of the observed drift times to the CCS of the AOTNa non-covalent aggregates was achieved by collecting, under the same experimental conditions, the drift times of a range of singly and multiply charged polyalanine peptides whose CCS had been obtained by conventional ion mobility spectrometry. Together with an obvious increase of the aggregate cross-section with the aggregation number, it was found that the aggregate cross-section increases with the charge state due to the sodium counterions steric effect and the augmented electrostatic repulsion. This finding is consistent with the result of a previous molecular dynamics study on positively charged AOTNa aggregates in the gas phase showing that, by increasing the charge state, the aggregates become progressively more oblate; implying a rise of their CCS. Moreover, the occurrence at each aggregation number and extra charge of a unique value of cross section points toward aggregates whose conformations do not show discernible shape change in the experiment time scale.
Analysis of New Synthetic Drugs by Ion Mobility Time-of-Flight Mass Spectrometry
Authors: Sysoev Alexey A. , Poteshin Sergey S. , Chernyshev Denis M. , Karpov Alexander V. , Tuzkov Yuriy B. , Kyzmin Vyacheslav V. , Sysoev Alexander A.
Published: March 2014

Characteristic ion mobility mass spectrometry data, reduced mobility, and limits of detection (signal-to-noise ratio = 3) were determined for six synthetic drugs and cocaine by ion mobility time-of-flight mass spectrometry (IM-TOF-MS) with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). The studied synthetic illicit drugs recently appeared on the recreational drug market as designer drugs and were methylone, 4-MEC (4′-methylethcathinone), 3,4-MDPV (3,4-methylenedioxypyrovalerone), JWH-210 [4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone], JWH-250 [2-(2-methoxyphenyl)-1-(1-pentyl-1H-indol-3-yl)ethanone], and JWH-203 [1-pentyl-3-(2′-chlorophenylacetyl) indole]. Absolute reduced mobilities in nitrogen were 1.35, 1.28, 1.41, 1.30, 1.18, 0.98, 1.09, and 1.07 cm2 V−1 s−1, for methylone [M–H]+, methylone [M+H]+, 4-MEC [M–H]+, 4-MEC [M+H]+, 3,4-MDPV [M+H]+, JWH-210 [M+H]+, JWH-250 [M+H]+, and JWH-203 [M+H]+, respectively. Selected illicit drugs are easily identified by IM-TOF-MS during a 100 s analysis. Relative limits of detection ranged from 4 to 400 nM are demonstrated for these compounds. Such relative limits of detection correspond to 14 pg to 2 ng absolute limits of detection. Better detection limits are obtained in APCI mode for all the illicit drugs except cocaine. ESI mode was found to be preferable for the IM-TOF-MS detection of cocaine at trace levels. A single sample analysis is completed in an order of magnitude less time than that for conventional liquid chromatography/mass spectrometry approach. The application allows one to consider IM-TOF-MS as a good candidate for a method to determine quickly the recently surfaced designer drugs marketed on the internet as “bath salts,” “spice,” and “herbal blends”.
Account: An Introduction to Velocity-Map Imaging Mass Spectrometry (VMImMS)
Authors: Bull James N. , Lee Jason W.L. , Gardiner Sara H. , Vallance Claire
Published: March 2014

This account introduces a new variant of time-of-flight mass spectrometry, termed velocity-map imaging mass spectrometry (VMImMS). While the ion abundances recorded in conventional ToF-MS measurements are highly useful for molecular quantification and structure determination, the final parent and fragment ion yields are largely blind to the dynamics of the processes in which the ions were formed inside the mass spectrometer. By recording the velocity distribution of each ion in tandem with the mass spectrum, not only can the details of the dissociative ionisation dynamics be unravelled, but the extra dimensions of information can be used for enhanced molecular fingerprinting, separating contributions from ions with identical mass-to-charge ratio and resolving components within mixtures, to name but a few examples. Measuring ion-velocity distributions within a mass spectrometry measurement is not new, but incorporating imaging techniques developed within the reaction dynamics community provides vastly improved velocity resolution for all ions simultaneously in a single-stage instrument. This account provides an introduction to VMImMS, outlines the fundamental instrumentation and detector requirements and the challenges associated with developing the method further, and details proof-of-concept work from our laboratory on a number of potential applications of the technique.
Wide-Range Mass Calibration for Negative-Ion DART Mass Spectrometry
Authors: Gross Jürgen H.
Published: March 2014

A method for accurate mass calibration covering a wide m/z range in negative-ion direct analysis in real time mass spectrometry (DART-MS) is described. It is based on a commercially available tuning solution (Agilent ES tune mix) normally applied in electrospray ionization. This acetonitrile solution is composed of ammonium trifluoroacetate, betaine, 2,4,6-tris(heptafluoropropyl)-1,3,5-triazine, and various symmetrical hexakis-(fluoroalkoxy)-phosphazenes. Upon addition of 2% (v/v) trifluoroacetic acid in negative-ion DART-MS, this mixture yields negative ions covering a range of m/z 69 to m/z 2834. Validity of the calibration procedure is demonstrated on a Fourier transform ion cyclotron resonance mass spectrometer by application to polyethylene glycol diacid and [60]fullerene. Experimental conditions and a mass reference list are provided.
Letter: Study on the Mechanism of Ferrite-Induced Dinitrophenol Photodegradation
Authors: Zaharia Marius , Borhan Adrian , Gherca Daniel , Pui Aurel , Gradinaru Robert , Zbancioc Gheorghita , Drochioiu Gabi
Published: March 2014

We report here the effectiveness of gas chromatography mass spectrometry techniques in establishing the ferrite-associated photocatalytic degradation mechanism of pesticide 2,4-dinitrophenol (2,4-DNP). Unlike the previously discussed DNP-degradation mechanisms that involve either oxidation or reduction reactions, ferrite-based ultraviolet (UV) photodegradation of DNP affords the nontoxic 6-hydroxy-3,5-dinitrohexa-2,4-dienal by an unusual water addition to the benzene core. We searched for and demonstrated the presence of an epoxide of DNP within the photodegradation process, which may unambiguously explain the novel photochemical mechanism. During the 15 min UV photoinduced process, DNP degradation efficiency on the zinc ferrite catalyst was calculated to be 82%, whereas the first-order kinetic rate constant k was as high as 3.4 × 10−2 min−1.
Design, Simulation and Evaluation of Improved Air Amplifier Incorporating an Ion Funnel for Nano-ESI MS
Authors: Jurčíček Petr , Liu Lingpeng , Zou Helin , An Zhiqi , Xiao Hongbin
Published: March 2014

An improved air amplifier design that takes advantage of the combined effects of aerodynamic and electrodynamic focusing was developed to couple a nanoelectrospray ionisation (nano-ESI) source and the heated mass spectrometer inlet to improve the sensitivity of a mass spectrometer. The new design comprises an electrodynamic ion funnel integrated into the main air pathway of the air amplifier to more effectively focus and transmit gas-phase ions from the nano-ESI source into the heated mass spectrometer inlet. Numerical computational fluid dynamics simulations were carried out using a commercial software package, ANSYS FLUENT, to provide more detailed information about the device's performance. The gas flow field as well as the electric field patterns and the Lagrangian ion motion were conveniently simulated using this single package and custom-written, user-defined functions. Experimental results show a nearly five-fold improvement in reserpine ion intensity with the air amplifier operated at a nitrogen gauge pressure of 40 kPa and no direct current (DC) or radiofrequency (RF) potentials applied to the ion funnel when the distance between the electrospray emitter and sampling inlet tube was 24 mm, as compared to direct sample infusion from the same distance without the air amplifier. More importantly, a nearly three-fold additional gain in ion intensity was measured when both DC and RF potentials were co-applied, resulting in more than a 13-fold overall ion intensity gain which could be attributed to the combined air amplifier aerodynamic and ion funnel electrodynamic focusing effect.
Utilisation of Gas-Phase Ion—Molecule Reactions for Differentiation between Phospho- and Sulfocarbohydrates
Authors: Piatkivskyi Andrii , Pyatkivskyy Yuriy , Hurt Matt , Ryzhov Victor
Published: March 2014

Gas-phase ion-molecule reactions of four boron-containing neutrals were explored as a means for differentiation between isobaric phospho- and sulfocarbohydrates. Phosphorylation and sulfation impose an addition of 80 Da to the molecular mass, so for low-resolution mass spectrometers compounds that have such modifications will appear at the same nominal mass-to-charge ( m/z) ratio. However, the ions of these isobaric species behave differently in ion–molecule reactions. All four evaluated neutral molecules [trimethyl borate (TMB), triethyl borate (TEB), diethylmethoxyborane (DEMB) and diisopropoxymethylborane (DIPMB)] proved to be reactive towards phosphorylated sugars and unreactive towards sulfated carbohydrates. In addition, TMB and TEB were found suitable for distinguishing positional isomers of phosphorylated carbohydrates, while reactions with DEMB and DIPMB were successful in differentiating phosphorylated, sulfated and unmodified deprotonated sugars. Similar reactions in the positive ion mode (alkali cationised) were found to be less conclusive.
Mod-seq: high-throughput sequencing for chemical probing of RNA structure
Authors: Talkish Jason , May Gemma , Lin Yizhu , Woolford John L. , McManus C. Joel
Published: March 2014

The functions of RNA molecules are intimately linked to their ability to fold into complex secondary and tertiary structures. Thus, understanding how these molecules fold is essential to determining how they function. Current methods for investigating RNA structure often use small molecules, enzymes, or ions that cleave or modify the RNA in a solvent-accessible manner. While these methods have been invaluable to understanding RNA structure, they can be fairly labor intensive and often focus on short regions of single RNAs. Here we present a new method (Mod-seq) and data analysis pipeline (Mod-seeker) for assaying the structure of RNAs by high-throughput sequencing. This technique can be utilized both in vivo and in vitro, with any small molecule that modifies RNA and consequently impedes reverse transcriptase. As proof-of-principle, we used dimethyl sulfate (DMS) to probe the in vivo structure of total cellular RNAs inSaccharomyces cerevisiae. Mod-seq analysis simultaneously revealed secondary structural information for all four ribosomal RNAs and 32 additional noncoding RNAs. We further show that Mod-seq can be used to detect structural changes in 5.8S and 25S rRNAs in the absence of ribosomal protein L26, correctly identifying its binding site on the ribosome. While this method is applicable to RNAs of any length, its high-throughput nature makes Mod-seq ideal for studying long RNAs and complex RNA mixtures.
Close the Gaps: A Learning-While-Doing Algorithm for Single-Product Revenue Management Problems
Authors: Wang Zizhuo , Deng Shiming , Ye Yinyu
Published: March 2014

We consider a retailer selling a single product with limited on-hand inventory over a finite selling season. Customer demand arrives according to a Poisson process, the rate of which is influenced by a single action taken by the retailer (such as price adjustment, sales commission, advertisement intensity, etc.). The relationship between the action and the demand rate is not known in advance. However, the retailer is able to learn the optimal action on the fly as she maximizes her total expected revenue based on the observed demand reactions.

Using the pricing problem as an example, we propose a dynamic learning-while-doing algorithm that only involves function value estimation to achieve a near-optimal performance. Our algorithm employs a series of shrinking price intervals and iteratively tests prices within that interval using a set of carefully chosen parameters. We prove that the performance of our algorithm is among the best of all possible algorithms in terms of the asymptotic regret (the relative loss compared to the full information optimal solution). Our result closes the performance gaps between parametric and nonparametric learning and between the post-price mechanism and the customer-bidding mechanism. Important managerial insight from this research is that the values of information on both the parametric form of the demand function as well as each customer's exact reservation price are less important than prior literature suggests. Our results also suggest that firms would be better off to perform dynamic learning and action concurrently rather than sequentially.
Conceptual tools for the description and acquisition of the German posture verb sitzen
Authors: De Knop Sabine
Published: March 2014

The study of German posture verbs has attracted the interest of many linguists, e.g. Berthele (2004 and 2006), Fagan (1991), Kutscher-Schultze-Berndt (2007) and Serra-Borneto (1996). It is surprising that most studies disregard the posture verb

The study aims at making up for these deficits. With examples from the German corpora from the Digitales Wörterbuch der Deutschen Sprache (DWDS), it first describes the different uses of the verb

In the framework of Cognitive Linguistics the study also proposes some ‘conceptual tools’ to facilitate the learning of the more abstract uses of the verb sitzen. These tools are semantic networks, visuals, and conceptual metaphors. Spatial distinctions such as those between container and contact are extended to more abstract areas of experience, especially in the context of situations describing abstract states. Here one of the main issues for the learner is to find out whether the abstract goal is conceptualized as a container, a contact or still another basic spatial relation. The efficiency of these conceptual tools is tested with a cloze test conducted with French-speaking students.
Combining experimental data and corpus data: Intermediate French-speaking learners and the English present
Authors: Littré Damien
Published: March 2014

This study combines experimental data and corpus data to describe how intermediate French-speaking learners of English perceive and (mis-)use the English present simple and present progressive.

A first part of this study reports the results from an interpretation task conducted with first year, French-speaking, English language and literature university students (n = 75). With some exceptions, students were found to show greater acceptance of more prototypical prompts. They also exhibited higher certainty with these prompts.

The second part of the study examines productive data from LONGDALE, a new longitudinal database of learner writing and speaking. Using annotated data for first year students, errors involving the present simple and progressive were extracted and classified in light of the interpretation task. Students were found to still make errors involving basic functions of the simple and progressive, as well as other errors that might be amenable to teaching.

Finally, pedagogical implications are discussed.