Wave reflection and cut-off frequencies in coupled FE-peridynamic grids

International Journal for Numerical Methods in Engineering Published by John Wiley & Sons, Ltd. Reflections are typically observed when pulses propagate across interfaces. Accordingly, spurious reflections might occur at the interfaces between different models used to simulate the same medium. Examples of such coupled models include classical continuum descriptions with molecular dynamics or peridynamic (PD) grids. In this work, three different coupling approaches are implemented to couple bond-based PDs with finite element (FE) solvers for solid mechanics. It is observed that incorporation of an overlapping zone, over which the coupling between FE and PD occurs, can lead to minimization of the reflected energy compared to a standard force coupling at the FE domain/PD grid interface. However, coupling with other existing methodologies, like the addition of ghost particles, achieves comparable accuracy at lower computational cost. Furthermore, the prudent selection of the discretization parameters is of pivotal importance as they control the high frequency cut-off limit. Mismatch between the cut-off frequencies of the different descriptions can lead to unrealistic results

A strategic assessment of cervical cancer prevention and treatment services in 3 districts of Uttar Pradesh, India

BACKGROUND: Despite being a preventable disease, cervical cancer claims the lives of almost half a million women worldwide each year. India bears one-fifth of the global burden of the disease, with approximately 130,000 new cases a year. In an effort to assess the need and potential for improving the quality of cervical cancer prevention and treatment services in Uttar Pradesh, a strategic assessment was conducted in three of the state's districts: Agra, Lucknow, and Saharanpur. METHODS: Using an adaptation of stage one of the World Health Organization's Strategic Approach to Improving Reproductive Health Policies and Programmes, an assessment of the quality of cervical cancer services was carried out by a multidisciplinary team of stakeholders. The assessment included a review of the available literature, observations of services, collection of hospital statistics and the conduct of qualitative research (in-depth interviews and focus group discussions) to assess the perspectives of women, providers, policy makers and community members. RESULTS: There were gaps in provider knowledge and practices, potentially attributable to limited provider training and professional development opportunities. In the absence of a state policy on cervical cancer, screening of asymptomatic women was practically absent, except in the military sector. Cytology-based cancer screening tests (i.e. pap smears) were often used to help diagnose women with symptoms of reproductive tract infections but not routinely screen asymptomatic women. Access to appropriate treatment of precancerous lesions was limited and often inappropriately managed by hysterectomy in many urban centers. Cancer treatment facilities were well equipped but mostly inaccessible for women in need. Finally, policy makers, community members and clients were mostly unaware about cervical cancer and its preventable nature, although with information, expressed a strong interest in having services available to women in their communities. CONCLUSION: To address gaps in services and unmet needs, state policies and integrated interventions have the potential to improve the quality of services for prevention of cervical cancer in Uttar Pradesh

Clostridium difficile Infections amongst Patients with Haematological Malignancies: A Data Linkage Study

OBJECTIVES: Identify risk factors for Clostridium difficile infection (CDI) and assess CDI outcomes among Australian patients with a haematological malignancy. METHODS: A retrospective cohort study involving all patients admitted to hospitals in Western Australia with a haematological malignancy from July 2011 to June 2012. Hospital admission data were linked with all hospital investigated CDI case data. Potential risk factors were assessed by logistic regression. The risk of death within 60 and 90 days of CDI was assessed by Cox Proportional Hazards regression. RESULTS: There were 2085 patients of whom 65 had at least one CDI. Twenty percent of CDI cases were either community-acquired, indeterminate source or had only single-day admissions in the 28 days prior to CDI. Using logistic regression, having acute lymphocytic leukaemia, neutropenia and having had bacterial pneumonia or another bacterial infection were associated with CDI. CDI was associated with an increased risk of death within 60 and 90 days post CDI, but only two deaths had CDI recorded as an antecedent factor. Ribotyping information was available for 33 of the 65 CDIs. There were 19 different ribotypes identified. CONCLUSIONS: Neutropenia was strongly associated with CDI. While having CDI is a risk factor for death, in many cases it may not be a direct contributor to death but may reflect patients having higher morbidity. A wide variety of C. difficile ribotypes were found and community-acquired infection may be under-estimated in these patients

Mechanically activated catalyst mixing for high-yield boron nitride nanotube growth

Boron nitride nanotubes (BNNTs) have many fascinating properties and a wide range of applications. An improved ball milling method has been developed for high-yield BNNT synthesis, in which metal nitrate, such as Fe(NO(3))(3), and amorphous boron powder are milled together to prepare a more effective precursor. The heating of the precursor in nitrogen-containing gas produces a high density of BNNTs with controlled structures. The chemical bonding and structure of the synthesized BNNTs are precisely probed by near-edge X-ray absorption fine structure spectroscopy. The higher efficiency of the precursor containing milling-activated catalyst is revealed by thermogravimetric analyses. Detailed X-ray diffraction and X-ray photoelectron spectroscopy investigations disclose that during ball milling the Fe(NO(3))(3) decomposes to Fe which greatly accelerates the nitriding reaction and therefore increases the yield of BNNTs. This improved synthesis method brings the large-scale production and application of BNNTs one step closer

IRE1α–XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity

Tumours evade immune control by creating hostile microenvironments that perturb T cell metabolism and effector function 1?4 . However, it remains unclear how intra-tumoral T cells integrate and interpret metabolic stress signals. Here we report that ovarian cancer?an aggressive malignancy that is refractory to standard treatments and current immunotherapies 5?8 ?induces endoplasmic reticulum stress and activates the IRE1α?XBP1 arm of the unfolded protein response 9,10 in T cells to control their mitochondrial respiration and anti-tumour function. In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression. Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α?XBP1 activation that suppressed mitochondrial activity and IFNγ production. Mechanistically, induction of XBP1 regulated the abundance of glutamine carriers and thus limited the influx of glutamine that is necessary to sustain mitochondrial respiration in T cells under glucose-deprived conditions. Restoring N-linked protein glycosylation, abrogating IRE1α?XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites. XBP1-deficient T cells in the metastatic ovarian cancer milieu exhibited global transcriptional reprogramming and improved effector capacity. Accordingly, mice that bear ovarian cancer and lack XBP1 selectively in T cells demonstrate superior anti-tumour immunity, delayed malignant progression and increased overall survival. Controlling endoplasmic reticulum stress or targeting IRE1α?XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.Fil: Song, Minkyung. Weill Cornell Medicine; Estados UnidosFil: Sandoval, Tito A.. Weill Cornell Medicine; Estados UnidosFil: Chae, Chang-Suk. Weill Cornell Medicine; Estados UnidosFil: Chopra, Sahil. Weill Cornell Medicine; Estados UnidosFil: Tan, Chen. Weill Cornell Medicine; Estados UnidosFil: Rutkowski, Melanie R.. University of Virginia; Estados UnidosFil: Raundhal, Mahesh. Dana Farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados UnidosFil: Chaurio, Ricardo A.. H. Lee Moffitt Cancer Center & Research Institute; Estados UnidosFil: Payne, Kyle K.. H. Lee Moffitt Cancer Center & Research Institute; Estados UnidosFil: Konrad, Csaba. Weill Cornell Medicine; Estados UnidosFil: Bettigole, Sarah E.. Quentis Therapeutics Inc.; Estados UnidosFil: Shin, Hee Rae. Quentis Therapeutics Inc.; Estados UnidosFil: Crowley, Michael J. P.. Weill Cornell Graduate School of Medical Sciences; Estados UnidosFil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Kossenkov, Andrew V.. The Wistar Institute; Estados UnidosFil: Motorykin, Ievgen. Weill Cornell Medicine,; Estados UnidosFil: Zhang, Sheng. Weill Cornell Medicine,; Estados UnidosFil: Manfredi, Giovanni. Weill Cornell Medicine,; Estados UnidosFil: Zamarin, Dmitriy. Memorial Sloan Kettering Cancer Center; Estados UnidosFil: Holcomb, Kevin. Weill Cornell Medicine,; Estados UnidosFil: Rodriguez, Paulo C.. H. Lee Moffitt Cancer Center & Research Institute; Estados UnidosFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Conejo Garcia, Jose R.. H. Lee Moffitt Cancer Center & Research Institute; Estados UnidosFil: Glimcher, Laurie H.. Dana Farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados UnidosFil: Cubillos-Ruiz, Juan R.. Weill Graduate School Of Medical Sciences; Estados Unidos. Weill Graduate School Of Medical Sciences; Estados Unido

Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials

Background Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated. Methods In two double-blind, multicentre studies done in an outpatient setting, after a 4-week run-in, patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast 500 mu g or placebo once a day for 24 weeks, in addition to salmeterol (M2-127 study) or tiotropium (M2-128 study). The primary endpoint was change in prebronchodilator forced expiratory volume in 1s (FEV(1)). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128. Findings In the salmeterol plus roflumilast trial, 466 patients were assigned to and treated with roflumilast and 467 with placebo; in the tiotropium plus roflumilast trial, 371 patients were assigned to and treated with roflumilast and 372 with placebo. Compared with placebo, roflumilast consistently improved mean prebronchodilator FEV(1) by 49 mL (p<0.0001) in patients treated with salmeterol, and 80 mL (p<0.0001) in those treated with tiotropium. Similar improvement in postbronchodilator FEV(1) was noted in both groups. Furthermore, roflumilast had beneficial effects on other lung function measurements and on selected patient-reported outcomes in both groups. Nausea, diarrhoea, weight loss, and, to a lesser extent, headache were more frequent in patients in the roflumilast groups. These adverse events were associated with increased patient withdrawal. Interpretation Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients

Effects of physician-nurse substitution on clinical parameters: a systematic review and meta-analysis

BACKGROUND: Physicians' shortage in many countries and demands of high-quality and affordable care make physician-nurse substitution an appealing workforce strategy. The objective of this study is to conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing the impact of physician-nurse substitution in primary care on clinical parameters. METHODS: We systematically searched OVID Medline and Embase, The Cochrane Library and CINAHL, up to August 2012; selected peer-reviewed RCTs comparing physician-led care with nurse-led care on changes in clinical parameters. Study selection and data extraction were performed in duplicate by independent reviewers. We assessed the individual study risk of bias; calculated the study-specific and pooled relative risks (RR) or weighted mean differences (WMD); and performed fixed-effects meta-analyses. RESULTS: 11 RCTs (N = 30,247) were included; most were from Europe, generally small with higher risk of bias. In all studies, nurses provided care for complex conditions including HIV, hypertension, heart failure, cerebrovascular diseases, diabetes, asthma, Parkinson's disease and incontinence. Meta-analyses showed greater reductions in systolic blood pressure (SBP) in favour of nurse-led care (WMD -4.27 mmHg, 95% CI -6.31 to -2.23) but no statistically significant differences between groups in the reduction of diastolic blood pressure (DBP) (WMD -1.48 mmHg, 95%CI -3.05 to -0.09), total cholesterol (TC) (WMD -0.08 mmol/l, 95%CI -0.22 to 0.07) or glycosylated haemoglobin (WMD 0.12%HbAc1, 95%CI -0.13 to 0.37). Of other 32 clinical parameters identified, less than a fifth favoured nurse-led care while 25 showed no significant differences between groups. LIMITATIONS: disease-specific interventions from a small selection of healthcare systems, insufficient quantity and quality of studies, many different parameters. CONCLUSIONS: trained nurses appeared to be better than physicians at lowering SBP but similar at lowering DBP, TC or HbA1c. There is insufficient evidence that nurse-led care leads to better outcomes of other clinical parameters than physician-led care