bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linking System-Wide Impacts of RNA Polymerase Mutations to the Fitness Cost of Rifampin Resistance in Pseudomonas aeruginosa
Authors: Qi Qin , Preston Gail M. , MacLean R. Craig 
Published: December 2014

ABSTRACTFitness costs play a key role in the evolutionary dynamics of antibiotic resistance in bacteria by generating selection against resistance in the absence of antibiotics. Although the genetic basis of antibiotic resistance is well understood, the precise molecular mechanisms linking the genetic basis of resistance to its fitness cost remain poorly characterized. Here, we examine how the system-wide impacts of mutations in the RNA polymerase (RNAP) generpoBshape the fitness cost of rifampin resistance inPseudomonas aeruginosa. Rifampin resistance mutations reduce transcriptional efficiency, and this explains 76% of the variation in fitness amongrpoBmutants. The pleiotropic consequence ofrpoBmutations is that mutants show altered relative transcript levels of essential genes. We find no evidence that global transcriptional responses have an impact on the fitness cost of rifampin resistance as revealed by transcriptome sequencing (RNA-Seq). Global changes in the transcriptional profiles ofrpoBmutants compared to the transcriptional profile of the rifampin-sensitive ancestral strain are subtle, demonstrating that the transcriptional regulatory network ofP. aeruginosais robust to the decreased transcriptional efficiency associated withrpoBmutations. On a smaller scale, we find that rifampin resistance mutations increase the expression of RNAP due to decreased termination at an attenuator upstream fromrpoB, and we argue that this helps to minimize the cost of rifampin resistance by buffering against reduced RNAP activity. In summary, our study shows that it is possible to dissect the molecular mechanisms underpinning variation in the cost of rifampin resistance and highlights the importance of genome-wide buffering of relative transcript levels in providing robustness against resistance mutations.IMPORTANCEAntibiotic resistance mutations carry fitness costs. Relative to the characteristics of their antibiotic-sensitive ancestors, resistant mutants show reduced growth rates and competitive abilities. Fitness cost plays an important role in the evolution of antibiotic resistance in the absence of antibiotics; however, the molecular mechanisms underlying these fitness costs is not well understood. We applied a systems-level approach to dissect the molecular underpinnings of the fitness costs associated with rifampin resistance inP. aeruginosaand showed that most of the variation in fitness cost can be explained by the direct effect of resistance mutations on the enzymatic activity of the mutated gene. Pleiotropic changes in transcriptional profiles are subtle at a genome-wide scale, suggesting that the gene regulatory network ofP. aeruginosais robust in the face of the direct effects of resistance mutations.
Do exercises used in injury prevention programmes modify cutting task biomechanics? A systematic review with meta-analysis
Authors: Pappas Evangelos , Nightingale Elizabeth J , Simic Milena , Ford Kevin R , Hewett Timothy E , Myer Gregory D 
Published: December 2014

ObjectiveSome injury prevention programmes aim to reduce the risk of ACL rupture. Although the most common athletic task leading to ACL rupture is cutting, there is currently no consensus on how injury prevention programmes influence cutting task biomechanics. To systematically review and synthesise the scientific literature regarding the influence of injury prevention programme exercises on cutting task biomechanics.DesignThe three largest databases (Medline, EMBASE and CINAHL) were searched for studies that investigated the effect of injury prevention programmes on cutting task biomechanics. When possible meta-analyses were performed.ResultsSeven studies met the inclusion criteria. Across all studies, a total of 100 participants received exercises that are part of ACL injury prevention programmes and 76 participants served in control groups. Most studies evaluated variables associated with the quadriceps dominance theory. The meta-analysis revealed decreased lateral hamstrings electromyography activity (p≤0.05) while single studies revealed decreased quadriceps and increased medial hamstrings activity and decreased peak knee flexion moment. Findings from single studies reported that ACL injury prevention exercises reduce neuromuscular deficits (knee valgus moment, lateral trunk leaning) associated with the ligament and trunk dominance theories, respectively. The programmes we analysed appear most effective when they emphasise individualised biomechanical technique correction and target postpubertal women.ConclusionsThe exercises used in injury prevention programmes have the potential to improve cutting task biomechanics by ameliorating neuromuscular deficits linked to ACL rupture, especially when they emphasise individualised biomechanical technique correction and target postpubertal female athletes.
A cross-sectional examination of the mental health of homeless mothers: does the relationship between mothering and mental health vary by duration of homelessness?
Authors: Zabkiewicz Denise M , Patterson Michelle , Wright Alexandra 
Published: December 2014

ObjectivesThis study draws on baseline data from the At Home/Chez Soi demonstration project to examine the association between parenting status and mental health among homeless women and whether the association varies by duration of homelessness.SettingStructured interviews were conducted with participants in five cities across Canada including Moncton, Montreal, Toronto, Vancouver and Winnipeg.ParticipantsEligibility criteria included those with legal adult status, with a mental illness, and who lacked a regular, fixed shelter. All 713 women who participated in the larger project were selected for inclusion in this analysis.MeasuresThe mental health conditions of interest include depression, post-traumatic stress disorder (PTSD), alcohol dependence and substance dependence.ResultsThe relationship between parenting status and depression, as well as PTSD, varied by duration of homelessness. Among women who had been homeless for less than 2 years, no relationship was found between parenting status and depression, or PTSD. However, among women who had been homeless for 2 or more years, the odds of depression was twice as high among parenting women compared with others (aOR=2.05, p≤0.05). A similar relationship was found between parenting status and PTSD (aOR=2.03, p≤0.05). The odds of substance dependence was found to be 2.62 times greater among parenting women compared with others and this relationship did not vary by duration of homelessness (aOR=2.62; 95% CI 1.86 to 3.69). No relationship was found between parenting and alcohol dependence.ConclusionsOverall, the findings from this study suggest that there is a relationship between long-term homelessness and mothers’ risk of poor mental health. Given the multiple demands mothers face, a failure to recognise their unique needs is likely to contribute to intergenerational legacies of homelessness and mental health problems.Trial registration numberWorld Health Organization's International Clinical Trials Registry Platform (ISRCTN66721740andISRCTN57595077).
Characteristics, determinants and perspectives of experienced medical humanitarians: a qualitative approach
Authors: Asgary Ramin , Lawrence Katharine 
Published: December 2014

ObjectiveTo explore the characteristics, motivations, ideologies, experience and perspectives of experienced medical humanitarian workers.DesignWe applied a qualitative descriptive approach and conducted in-depth semistructured interviews, containing open-ended questions with directing probes, with 44 experienced international medical aid workers from a wide range of humanitarian organisations. Interviews were coded and analysed, and themes were developed.SettingInternational non-governmental organisations (INGOs) and United Nations (UN).Results61% of participants were female; mean age was 41.8 years with an average of 11.8 years of humanitarian work experience with diverse major INGOs. Significant core themes included: population's rights to assistance, altruism and solidarity as motives; self-identification with the mission and directives of INGOs; shared personal and professional morals fostering collegiality; accountability towards beneficiaries in areas of programme planning and funding; burnout and emotional burdens; uncertainties in job safety and security; and uneasiness over changing humanitarian principles with increasing professionalisation of aid and shrinking humanitarian access. While dissatisfied with overall aid operations, participants were generally satisfied with their work and believed that they were well-received by, and had strong relationships with, intended beneficiaries.ConclusionsDespite regular use of language and ideology of rights, solidarity and concepts of accountability, tension exists between the philosophy and practical incorporation of accountability into operations. To maintain a humanitarian corps and improve aid worker retention, strategies are needed regarding management of psychosocial stresses, proactively addressing militarisation and neo-humanitarianism, and nurturing individuals’ and organisations’ growth with emphasis on humanitarian principles and ethical practices, and a culture of internal debate, reflection and reform.
PSYCHOSOCIAL STRESS PARTIALLY MEDIATES THE ASSOCIATION BETWEEN RACE AND PRENATAL DEPRESSIVE SYMPTOMS IN A SAMPLE OF PREGNANT WOMEN IN ALBERTA
Authors: Roy A , Patten SB , Thurston WE , Tough S 
Published: December 2014

IntroductionPrenatal depression is a serious maternal-child health concern; risk factors and health consequences appear more prevalent in Aboriginal communities and ethnic minority groups. However, research on these populations is limited. We examined the following questions: A) How do pregnant Aboriginal women, ethnic minority women and White/Caucasian women compare on levels of depressive symptoms, and on major risk and protective factors? B) Is non-dominant race associated with higher depressive symptoms? C) Through what pathways may race operate to contribute to depressive symptoms?MethodsData were from theAll Our Babiesstudy (n=3354 pregnant women from Alberta recruited between 2008–2011). Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS). Descriptive statistics and multivariable regression methods were used to assess the following hypotheses: We hypothesized that Aboriginal and ethnic minority women would have significantly higher mean EPDS score estimates relative to White/Caucasian women. The association between race and EPDS score was hypothesized to be partially mediated by risk factors such as socioeconomic factors, health background factors, discrimination, domestic violence, and psychosocial stress. Potential confounders were age, marital status, and parity. Diet and social support were hypothesized as protective buffers between stress and depressive symptoms.ResultsWhite/Caucasian women appeared to have higher income, better employment and higher social support, and have significantly lower depressive symptoms. The association between race and depressive symptoms appeared partially mediated by socioeconomic factors and psychosocial stress; the attenuation with addition of stress in the model was particularly striking. However, race remained highly statistically significant as a predictor. Social support appeared to moderate the association between stress and depressive symptoms.ConclusionMental health disparities between pregnant White/Caucasian women and other women are driven by social disparities. A better understanding of the determinants of prenatal depression in specific populations may facilitate more effective public health and clinical interventions.
REVIEW OF CARDIOVASCULAR DISEASE PRIMARY PREVENTION INTERVENTIONS IN LOW- AND MIDDLE-INCOME COUNTRIES
Authors: Park J , Oremus M 
Published: December 2014

BackgroundThe burden of cardiovascular diseases (CVD) in low- and middle-income countries (LMIC) has increased greatly. Primary prevention of CVD has been shown to work in developed countries, and is urgently needed in LMIC.ObjectiveThis literature review aims to evaluate the effectiveness of primary prevention strategies for CVD in LMIC.MethodsStudies were obtained via a detailed search using Ovid MEDLINE©, EMBASE and Global Health databases, published in English between 1946 and 2013. Included studies were primary research articles aimed at the primary prevention of CVD in LMIC participants over age 15 years. We included studies of interventions targeted to the general population or to groups with specific levels of risk for CVD.ResultsOf 1002 studies that were identified through the initial search, 12 studies met the inclusion criteria. The interventions at the general population level mainly consisted of health promotion and education through media, as well as policy implementation and community outreach. The risk-group focused interventions used pharmaceutical treatment of cardiovascular risk factors or CVD education and lifestyle counselling as preventive measures. All but two studies showed significant improvement in at least one cardiovascular risk factor. Primary prevention strategies used in high-risk groups showed greater benefits in reducing physiological cardiovascular risk factors when compared to population-based interventions.ConclusionPrimary prevention interventions have been shown to be effective at lowering cardiovascular risk factors in LMIC. In general, the included studies indicate that health promotion and education are the most successful prevention strategies. However, due to heterogeneity between the included studies (e.g. different populations or treatment modalities), no valid conclusions on the comparative effectiveness of specific study interventions can be made.
Enhanced Technology Mapping for FPGAs with Exploration of Cell Configurations
Authors: Zgheib Grace , Ouaiss Iyad 
Published: December 2014

In the state-of-the-art field-programmable gate arrays (FPGAs), logic circuits are synthesized and mapped on clusters of look-up tables. However, arithmetic operations benefit from an existing dedicated adder along with a carry chain used to ensure a fast carry propagation. This carry chain is a dedicated wire available in the architecture of the FPGA and is as such independent of the external programmable routing resources. In this paper, we propose a variable-structure Boolean matching technology mapper with embedded decomposition techniques to map nonarithmetic logic functions on carry chains. Previously synthesized and mapped logic functions are adapted so that their outputs are routed using the dedicated carry chains instead of the external programmable interconnects. The experimental results show a reduction in the used routing resources as well as the circuit area when using this Boolean matching-based mapper on the Altera Stratix-III FPGA.
Entanglement generation and dynamics for a Bose–Hubbard model in a double-well potential
Authors: Gentile F. , Montorsi A. , Roncaglia M. 
Published: December 2014

The study of entanglement between bosonic systems is of primary importance for establishing feasible resources needed for implementing quantum information protocols, both in their interacting atomic or photonic realizations. Atomic systems are particularly efficient in the production of large amounts of entanglement, providing higher information density than conventional qubit entangled states. Such increased quantum resources pave the way to novel fundamental tests of nature and efficient applications in quantum information, metrology and sensing. We consider a basic setup made up of two parties A and B, each one populated by a single level bosonic variable. The bosons are interacting and can hop between A and B, thus describing a two-site Bose–Hubbard Hamiltonian. We consider the generation of quantum states in several situations that cover the majority of physical realizations: ground state, finite temperature, unitary dynamics, dissipation through dephasing and loss of particles. The system is analyzed through truncated exact diagonalization, as a function of the microscopic parameters. The nonseparability of the obtained quantum states is estimated by means of the negativity, which has recently been proven to be a suitable measure of entanglement [M. Roncaglia, A. Montorsi and M. Genovese, Phys. Rev. A 90 (2014) 062303]. Finally, we calculate lower bounds of the entanglement of formation (EOF), an indicator that quantifies the minimal amount of entanglement resources needed to build up such states.
A Prospective Follow-up Study of the Relationship between C-Reactive Protein and Human Cancer Risk in the Chinese Kailuan Female Cohort
Authors: Wang Gang , Li Ni , Chang Sheng , Bassig Bryan A. , Guo Lanwei , Ren Jiansong , Su Kai , Li Fang , Chen Shuohua , Wu Shouling , Zou Yuhuan , Dai Min , Zheng Tongzhang , He Jie 
Published: December 2014

Abstract
Background: C-reactive protein (CRP) has been associated with cancer risk in some prospective studies. However, the associations have not been entirely consistent and have not been evaluated in Chinese females. We conducted a large population-based cohort study to investigate whether elevated levels of CRP at baseline are associated with an increased risk of cancer among Chinese females.
Methods: A total of 19,437 women from the Chinese Kailuan Female Cohort were enrolled in the study in July 2006. Levels of high-sensitivity CRP (hsCRP) were tested at baseline for all subjects. Multivariable Cox proportional hazards regression models were used to evaluate the association between levels of hsCRP and risk of all cancers, including breast cancer, lung cancer, colorectal cancer, and other cancers.
Results: By December 31, 2011, a total of 322 incident cancer cases accrued. Compared with women with lower hsCRP levels (&lt;1 mg/L), women with higher hsCRP (&gt;3 mg/L) had a significantly increased risk of all incident cancers [HR, 1.62; 95% confidence intervals (CI), 1.23–2.14; Ptrend = 0.001] and breast cancer (HR, 1.74; 95% CI, 1.01–2.97; Ptrend = 0.047). The significant association between hsCRP levels and breast cancer risk was apparent among younger women (&lt;50 years; HR, 2.76; 95% CI, 1.18–6.48).
Conclusion: Elevated levels of hsCRP at baseline may be associated with an increased risk of cancer, especially breast cancer, and particularly in younger Chinese women.
Impact: Our findings provide additional evidence for a role of inflammation in carcinogenesis and suggest that CRP may be a potentially useful biomarker of cancer risk in this population. Cancer Epidemiol Biomarkers Prev; 24(2); 459–65. ©2014 AACR.
ANG4043, a Novel Brain-Penetrant Peptide–mAb Conjugate, Is Efficacious against HER2-Positive Intracranial Tumors in Mice
Authors: Regina Anthony , Demeule Michel , Tripathy Sasmita , Lord-Dufour Simon , Currie Jean-Christophe , Iddir Mustapha , Annabi Borhane , Castaigne Jean-Paul , Lachowicz Jean E. 
Published: December 2014

Abstract
Anti-HER2 monoclonal antibodies (mAb) have been shown to reduce tumor size and increase survival in patients with breast cancer, but they are ineffective against brain metastases due to poor brain penetration. In previous studies, we identified a peptide, known as Angiopep-2 (An2), which crosses the blood–brain barrier (BBB) efficiently via receptor-mediated transcytosis, and, when conjugated, endows small molecules and peptides with this property. Extending this strategy to higher molecular weight biologics, we now demonstrate that a conjugate between An2 and an anti-HER2 mAb results in a new chemical entity, ANG4043, which retains in vitro binding affinity for the HER2 receptor and antiproliferative potency against HER2-positive BT-474 breast ductal carcinoma cells. Unlike the native mAb, ANG4043 binds LRP1 clusters and is taken up by LRP1-expressing cells. Measuring brain exposure after intracarotid delivery, we demonstrate that the new An2–mAb conjugate penetrates the BBB with a rate of brain entry (Kin) of 1.6 × 10−3 mL/g/s. Finally, in mice with intracranially implanted BT-474 xenografts, systemically administered ANG4043 increases survival. Overall, this study demonstrates that the incorporation of An2 to the anti-HER2 mAb confers properties of increased uptake in brain endothelial cells as well as BBB permeability. These characteristics of ANG4043 result in higher exposure levels in BT-474 brain tumors and prolonged survival following systemic treatment. Moreover, the data further validate the An2–drug conjugation strategy as a way to create brain-penetrant biologics for neuro-oncology and other CNS indications. Mol Cancer Ther; 14(1); 129–40. ©2014 AACR.
Acute Hemodynamic Decompensation During Catheter Ablation of Scar-Related Ventricular Tachycardia
Authors: Santangeli Pasquale , Muser Daniele , Zado Erica S. , Magnani Silvia , Khetpal Sumun , Hutchinson Mathew D. , Supple Gregory , Frankel David S. , Garcia Fermin C. , Bala Rupa , Riley Michael P. , Lin David , Rame J. Eduardo , Schaller Robert , Dixit Sanjay , Marchlinski Francis E. , Callans David J. 
Published: December 2014

Background—
The occurrence of periprocedural acute hemodynamic decompensation (AHD) in patients undergoing radiofrequency catheter ablation of scar-related ventricular tachycardia (VT) has not been previously investigated.

Methods and Results—

We identified univariate predictors of periprocedural AHD in 193 consecutive patients undergoing radiofrequency catheter ablation of scar-related VT. AHD was defined as persistent hypotension despite vasopressors and requiring mechanical support or procedure discontinuation. AHD occurred in 22 (11%) patients. Compared with the rest of the population, patients with AHD were older (68.5±10.7 versus 61.6±15.0 years;
P
=0.037); had a higher prevalence of diabetes mellitus (36% versus 18%;
P
=0.045), ischemic cardiomyopathy (86% versus 52%;
P
=0.002), chronic obstructive pulmonary disease (41% versus 13%;
P
=0.001), and VT storm (77% versus 43%;
P
=0.002); had more severe heart failure (New York Heart Association class III/IV: 55% versus 15%,
P
<0.001; left ventricular ejection fraction: 26±10% versus 36±16%,
P
=0.003); and more often received periprocedural general anesthesia (59% versus 29%;
P
=0.004). At 21±7 months follow-up, the mortality rate was higher in the AHD group compared with the rest of the population (50% versus 11%, log-rank
P
<0.001).

Conclusions—
AHD occurs in 11% of patients undergoing radiofrequency catheter ablation of scar-related VT and is associated with increased risk of mortality over follow-up. AHD may be predicted by clinical factors, including advanced age, ischemic cardiomyopathy, more severe heart failure status (New York Heart Association class III/IV, lower ejection fraction), associated comorbidities (diabetes mellitus and chronic obstructive pulmonary disease), presentation with VT storm, and use of general anesthesia.