bluuebunny/crossref_metadata_2025 huggingface dataset:
MET Tyrosine Kinase Inhibition Enhances the Antitumor Efficacy of an HGF Antibody
Authors: Farrell Pamela J. , Matuszkiewicz Jennifer , Balakrishna Deepika , Pandya Shweta , Hixon Mark S. , Kamran Ruhi , Chu Shaosong , Lawson J. David , Okada Kengo , Hori Akira , Mizutani Akio , Iwata Hidehisa , de Jong Ron , Hibner Barbara , Vincent Patrick
Published: March 2017

Receptor tyrosine kinase therapies have proven to be efficacious in specific cancer patient populations; however, a significant limitation of tyrosine kinase inhibitor (TKI) treatment is the emergence of resistance mechanisms leading to a transient, partial, or complete lack of response. Combination therapies using agents with synergistic activity have potential to improve response and reduce acquired resistance. Chemoreagent or TKI treatment can lead to increased expression of hepatocyte growth factor (HGF) and/or MET, and this effect correlates with increased metastasis and poor prognosis. Despite MET's role in resistance and cancer biology, MET TKI monotherapy has yielded disappointing clinical responses. In this study, we describe the biological activity of a selective, oral MET TKI with slow off-rate and its synergistic antitumor effects when combined with an anti-HGF antibody. We evaluated the combined action of simultaneously neutralizing HGF ligand and inhibiting MET kinase activity in two cancer xenograft models that exhibit autocrine HGF/MET activation. The combination therapy results in additive antitumor activity in KP4 pancreatic tumors and synergistic activity in U-87MG glioblastoma tumors. Pharmacodynamic characterization of biomarkers that correlate with combination synergy reveal that monotherapies induce an increase in the total MET protein, whereas combination therapy significantly reduces total MET protein levels and phosphorylation of 4E-BP1. These results hold promise that dual targeting of HGF and MET by combining extracellular ligand inhibitors with intracellular MET TKIs could be an effective intervention strategy for cancer patients who have acquired resistance that is dependent on total MET protein. Mol Cancer Ther; 16(7); 1269–78. ©2017 AACR.
Safety and Efficacy of Flexible Ureteroscopy in Combination with Holmium Laser Lithotripsy for the Treatment of Bilateral Upper Urinary Tract Calculi
Authors: Yang Bing , Ning Hao , Liu Zheng , Zhang Yi , Yu Chengfan , Zhang Xianghua , Pan Dongliang , Ding Kejia
Published: March 2017

Objective: To retrospectively evaluate the safety and efficacy of flexible ureteroscopy (FURS) in combination with holmium laser lithotripsy for the treatment of bilateral upper urinary calculi. Materials and Methods: The stone-free status was defined as the absence of any stones or asymptomatic status, or the presence of clinically insignificant residual fragments <4 mm, and was assessed by plain kidney, ureter, and bladder X-ray. The operative time, stone-free rates (SFRs), serum creatinine (SCr), and complications were recorded. Results: During the operation, there was no bleeding, ureteral perforation, avulsion, and rupture. Postoperative hematuria was observed in 2 patients. SCr increased significantly on the first day after the procedure compared with the preoperative SCr, but after 4 weeks, the renal function significantly improved (p < 0.05). The SFR was 71.6% (63/88) on the first day after the first surgical procedure; it then increased to 86.4% (76/88) in the fourth week, and rose to 97.4% (76/78) after the second operation. Conclusion: The results demonstrated that FURS in combination with holmium laser lithotripsy represented a favorable less-invasive alternative with high SFR and acceptable complication rates in the treatment of bilateral upper urinary tract calculi.
Clinical Trial of Vadadustat in Patients with Anemia Secondary to Stage 3 or 4 Chronic Kidney Disease
Authors: Martin Edouard R. , Smith Mark T. , Maroni Bradley J. , Zuraw Qing C. , deGoma Emil M.
Published: March 2017

Background: Therapeutic options for the treatment of anemia secondary to chronic kidney disease (CKD) remain limited. Vadadustat (AKB-6548) is an oral hypoxia-inducible factor prolyl-hydroxylase domain (HIF-PHD) inhibitor that is being investigated for the treatment of anemia secondary to CKD. Methods: A phase 2a, multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial (NCT01381094) was undertaken in adults with anemia secondary to CKD stage 3 or 4. Eligible subjects were evenly randomized to 5 groups: 240, 370, 500, or 630 mg of once-daily oral vadadustat or placebo for 6 weeks. All subjects received low-dose supplemental oral iron (50 mg daily). The primary endpoint was the mean absolute change in hemoglobin (Hb) from baseline to the end of treatment. Secondary endpoints included iron indices, safety, and tolerability. Results: Ninety-three subjects were randomized. Compared with placebo, vadadustat significantly increased Hb after 6 weeks in a dose-dependent manner (analysis of variance; p < 0.0001). Vadadustat increased the total iron-binding capacity and decreased concentrations of ferritin and hepcidin. The proportion of subjects with at least 1 treatment-emergent adverse event was similar between vadadustat- and placebo-treated groups. No significant changes in blood pressure, vascular endothelial growth factor, C-reactive protein, or total cholesterol were observed. Limitations of this study included its small sample size and short treatment duration. Conclusions: Vadadustat increased Hb levels and improved biomarkers of iron mobilization and utilization in patients with anemia secondary to stage 3 or 4 CKD. Global multicenter, randomized phase 3 trials are ongoing in non-dialysis-dependent and dialysis-dependent patients.
Aspirin and Risk of Subarachnoid Hemorrhage
Authors: Phan Kevin , Moore Justin M. , Griessenauer Christoph J. , Ogilvy Christopher S. , Thomas Ajith J.
Published: March 2017

Background and Purpose—

Recent studies have suggested that the use of low-dose aspirin may reduce the risk of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to evaluate any association between aspirin use and risk of aSAH based on the literature, and whether this is influenced by duration or frequency of aspirin use.

Methods—

A search of electronic databases was done from inception to September 2016. For each study, data on risk of aSAH in aspirin versus nonaspirin users were used to generate odds ratios and 95% confidence intervals, and combined using inverse variance–weighted averages of logarithmic odds ratios in a random-effects models.

Results—

From 7 included studies, no significant difference was noted between aspirin use of any duration or frequency and nonaspirin users (odds ratio, 1.00; 95% confidence interval, 0.81–1.24;
P
=0.99). We found a significant association between short-term use of aspirin (<3 months) and the risk of aSAH (odds ratio, 1.61; 95% confidence interval, 1.20–2.18;
P
=0.002). No significant difference was found in terms of risk of aSAH for 3 to 12 months, 1 to 3 years, and >3 years of durations of use. No significant association was found between infrequent aspirin use (≤2× per week) or frequent use (≥3× per week) with risk of aSAH.

Conclusions—

Current evidence suggests that short-term (<3 months) use of aspirin is associated with increased risk of aSAH. Limitations include substantial heterogenity of the included studies. The role of long-term aspirin in reducing risk of aSAH remains unclear and ideally should be addressed by an appropriately designed randomized controlled trial.
The Temporal Modulation Structure of Infant-Directed Speech
Authors: Leong Victoria , Kalashnikova Marina , Burnham Denis , Goswami Usha
Published: March 2017

The temporal modulation structure of adult-directed speech (ADS) is thought to be encoded by neuronal oscillations in the auditory cortex that fluctuate at different temporal rates. Oscillatory activity is thought to phase-align to amplitude modulations in speech at corresponding rates, thereby supporting parsing of the signal into linguistically relevant units. The temporal modulation structure of infant-directed speech (IDS) is unexplored. Here we compare the amplitude modulation (AM) structure of IDS recorded from mothers speaking, over three occasions, to their 7-, 9-, and 11-month-old infants, and the same mothers speaking ADS. Analysis of the modulation spectrum in each case revealed that modulation energy in the theta band was significantly greater in ADS than in IDS, whereas in the delta band, modulation energy was significantly greater for IDS than ADS. Furthermore, phase alignment between delta- and theta-band AMs was stronger in IDS compared to ADS. This remained the case when IDS and ADS were rate-normalized to control for differences in speech rate. These data indicate stronger rhythmic synchronization and acoustic temporal regularity in IDS compared to ADS, structural acoustic differences that may be important for early language learning.
Bellendenker gen. nov., a new Australian genus of Glandulariini (Coleoptera: Staphylinidae: Scydmaeninae)
Authors: JAŁOSZYŃSKI PAWEŁ
Published: March 2017

Bellendenker palpalis gen. et sp. nov. is described based on specimens collected in northeastern Australia. The genus is unique among glandulariine Scydmaeninae in strikingly elongated labial palps, which are longer than the labium; no modifications of labial palps have been known so far in this large tribe. Bellendenker is most similar to the Australian genus Scydmaenozila Jałoszyński, they share similar thoracic structures. Numerous differences in cephalic characters can be used to distinguish these genera; moreover, adults of Bellendenker are wingless and have reduced structures of the elytral base. Fourteen genera of Glandulariini (plus one of unclear status, known only from original description) are currently known to occur in Australia, eight being endemic to this continent.
Energetics of Deep Alpine Valleys in Pooling and Draining Configurations
Authors: Arduini Gabriele , Chemel Charles , Staquet Chantal
Published: March 2017

The Weather Research and Forecasting Model is used to investigate the nocturnal atmospheric boundary layer in a valley that opens either on a wider valley (draining configuration) or on a narrower valley (pooling configuration). One draining case and three weak to strong pooling cases are considered. Results show that the structure of the nocturnal boundary layer is substantially different for the draining and pooling configurations. Greater pooling corresponds with a deeper and colder boundary layer. Down-valley winds are weaker for pooling and draining configurations than in an equivalent valley opening directly on a plain. For the strong pooling case, an up-valley flow develops from the narrower to the wider valley during the evening transition, affecting the mass budget of the wider valley during that period. Considering the heat budget of the valley system, the contribution of the diabatic processes, when appropriately weighted, hardly varies along the valley axis. Conversely, the contribution of advection varies along the valley axis: it decreases for a pooling configuration and increases for a draining configuration. Consequently, for a pooling configuration, the heat transfer between the valley and the plain is reduced, thereby increasing the temperature difference between them. For the strong pooling case, this temperature difference can be explained by the valley-volume effect once the down-valley flow has developed. This occurs in a valley when the “extra” heat loss within the valley due to the surface sensible heat flux balances the heat input due to advection.
Large Increase in Incident Shortwave Radiation due to the Ozone Hole Offset by High Climatological Albedo over Antarctica
Authors: Chiodo G. , Polvani L. M. , Previdi M.
Published: March 2017

Despite increasing scientific scrutiny in recent years, the direct impact of the ozone hole on surface temperatures over Antarctica remains uncertain. Here, this question is explored by using the Community Earth System Model–Whole Atmosphere Community Climate Model (CESM-WACCM), contrasting two ensembles of runs with and without stratospheric ozone depletion. It is found that, during austral spring, the ozone hole leads to a surprisingly large increase in surface downwelling shortwave (SW) radiation over Antarctica of 3.8 W m−2 in clear sky and 1.8 W m−2 in all sky. However, despite this large increase in incident SW radiation, no ozone-induced surface warming is seen in the model. It is shown that the lack of a surface temperature response is due to reflection of most of the increased downward SW, resulting in an insignificant change to the net SW radiative heating. To first order, this reflection is simply due to the high climatological surface albedo of the Antarctic snow (97% in visible SW), resulting in a net zero ozone-induced surface SW forcing. In addition, it is shown that stratospheric ozone depletion has a negligible effect on longwave (LW) radiation and other components of the surface energy budget. These results suggest a minimal role for ozone depletion in forcing Antarctic surface temperature trends on a continental scale.
Impact of Anthropogenic Climate Change on the East Asian Summer Monsoon
Authors: Burke Claire , Stott Peter
Published: March 2017

The East Asian summer monsoon (EASM) is important for bringing rainfall to large areas of China. Historically, variations in the EASM have had major impacts including flooding and drought. The authors present an analysis of the impact of anthropogenic climate change on EASM rainfall in eastern China using a newly updated attribution system. The results suggest that anthropogenic climate change has led to an overall decrease in total monsoon rainfall over the past 65 years and an increased number of dry days. However, the model also predicts that anthropogenic forcings have caused the most extreme heavy rainfall events to become shorter in duration and more intense. With the potential for future changes in aerosol and greenhouse gas emissions, historical trends in monsoon rainfall may not be indicative of future changes, although extreme rainfall is projected to increase over East Asia with continued warming in the region.
Resurfacing of South Pacific Tropical Water in the Equatorial Pacific and Its Variability Associated with ENSO
Authors: Qu Tangdong , Gao Shan
Published: March 2017

Analysis of results from a simulated passive tracer confirms the resurfacing of South Pacific Tropical Water in the equatorial Pacific. Over the period of integration (1993–2011), both the volume and barycenter of the South Pacific Tropical Water that resurfaces in the equatorial Pacific are tightly linked to El Niño–Southern Oscillation (ENSO), with their correlation with the Niño-3.4 index reaching −0.79 and 0.84, respectively. Their correlation (−0.75 and 0.85) with the sea surface salinity index, Niño-S34.8, is also high. Of particular interest is that both the volume and barycenter of the resurfacing South Pacific Tropical Water peak earlier than the ENSO indices by about 3 months. On the interannual time scale, the resurfacing of South Pacific Tropical Water may modulate the sea surface salinity in the equatorial Pacific at a rate equivalent to as much as 25% of the surface freshwater flux. The results suggest that the resurfacing of South Pacific Tropical Water directly contributes to the sea surface salinity variability in the equatorial Pacific and potentially plays a role in ENSO evolution.
Mean Subsurface Upwelling Induced by Intraseasonal Variability over the Equatorial Indian Ocean
Authors: Ogata Tomomichi , Nagura Motoki , Masumoto Yukio
Published: March 2017

A possible formation mechanism of mean subsurface upwelling along the equator in the Indian Ocean is investigated using a series of hierarchical ocean general circulation model (OGCM) integrations and analytical considerations. In an eddy-resolving OGCM with realistic forcing, mean vertical velocity in the tropical Indian Ocean shows rather strong upwelling, with its maximum on the equator in the subsurface layer below the thermocline. Heat budget analysis exhibits that horizontal and vertical heat advection by deviations (i.e., due to deviations of velocity and temperature from the mean) balances with vertical advection caused by mean equatorial upwelling. Horizontal heat advection is mostly associated with intraseasonal variability with periods of 3–91 days, while contributions from longer periods (>91 days) are small. Sensitivity experiments with a coarse-resolution OGCM further demonstrate that such mean equatorial upwelling cannot be reproduced by seasonal forcing only. Adding the intraseasonal wind forcing, especially meridional wind variability with a period of 15 days, generates significant mean subsurface upwelling on the equator. Further experiments with idealized settings confirm the importance of intraseasonal mixed Rossby–gravity (MRG) waves to generate mean upwelling, which appears along the energy “beam” of the MRG wave. An analytical solution of the MRG waves indicates that wave-induced temperature advection caused by the MRG waves with upward (downward) phase propagation results in warming (cooling) on the equator. This wave-induced warming (cooling) is shown to balance with the mean equatorial upwelling (downwelling), which is consistent with simulated characteristics in the OGCM experiments.
Synthesis of Observations from the Precision Atmospheric Marine Boundary Layer Experiment (PreAMBLE)
Authors: Rahn David A. , Parish Thomas R. , Leon David
Published: March 2017

Research flights during the Precision Atmospheric Marine Boundary Layer Experiment (PreAMBLE) in Southern California during May–June 2012 focused on three main features found in the nearshore marine boundary layer (MBL): the coastal jet (10 flights), the Catalina eddy (3 flights), and the initiation of a southerly surge (1 flight). Several topics were examined with case studies, but results from individual events may not represent typical conditions. Although these flights do not constitute a long-term set of data, observations from PreAMBLE are used to find common features. Two main topics are addressed: the MBL collapse into the expansion fan, and the subsequent transition into the Santa Barbara Channel (SBC). The midmorning to late afternoon flights occur during moderate to strong northerly wind. Slope of the MBL in the expansion fan varies and wave perturbations can be embedded within the expansion fan. As the cool MBL flow turns into the SBC, it moves underneath a deeper and warmer MBL that originates from the southeast over the warmer ocean. The temperature inversion between the cool and warm MBL erodes toward the east until there is only the inversion between the warm MBL and free troposphere. The dissipation of the lower layer into the SBC observed by the aircraft differs from previous conceptual models that depict a continuous MBL that thins and then deepens again in the SBC, which was inferred from sparse observations and numerical simulations. Only one flight within the SBC detected a hydraulic jump from 100 to 200 m above the surface.
The 2016 Electoral Reform in Mongolia: From Mixed System and Multiparty Competition to FPTP and One-Party Dominance
Authors: Maškarinec Pavel
Published: March 2017

This article tests the effects of a new electoral system that was introduced in Mongolia for the June 2016 elections. The decision to implement a first-past-the-post (FPTP) system instead of a mixed-member majoritarian (MMM) system, which was first and last used in the previous elections of 2012, was due to the April 2016 ruling of the Mongolian Constitutional Court on unconstitutionality of the list tier as one of the mechanisms for distributing seats within MMM. Through an analysis of national- and district-level results, this article addresses the question whether electoral competition at the district level was consistent with Duverger’s law and resulted in the restoration of bipartism, which had been disrupted in 2012 due to the use of MMM.
Who Should the Military Recruit? The Effects of Institutional, Occupational, and Self-Enhancement Enlistment Motives on Soldier Identification and Behavior
Authors: Woodruff Todd D.
Published: March 2017

The U.S. military spends millions of dollars and substantial institutional effort to understand enlistment motives and appropriately target incentives, recruiting effort, and marketing to prospective members. Similarly, researchers have worked for decades to identify, understand, and conceptualize enlistment motives. Much less effort has been made to understand the effect enlistment motives/goals have on individuals after they join. This research uses well-established enlistment motives/goals to identify and understand their effects on soldiers’ value to the military in terms of organizational identification and critical discretionary behaviors. Using multicohort cross-sectional data from future, initial training, and currently serving soldiers, this research finds that intrinsic enlistment motives/goals, such as altruistic service and self-enhancement, create greater relational and behavioral value than most extrinsic/economic enlistment motives/goals such as pay, gaining skills for future employment, and educational funding. Intrinsic enlistment motives/goals have a strong positive effect on perceptions of the organization, social satisfaction, organizational identification, and discretionary pro-organizational behaviors. Conversely, economic enlistment goals tend to be associated with higher levels of economic satisfaction but decreased organizational identification and pro-organizational behavior. Importantly, these effects tend to persist among soldiers who have been in the military for years. Contrary to the institutional–occupational framework, self-focused enlistment goals, both intrinsic and extrinsic, can creative substantial value for the military when they are aligned with organizational interests. Based on these findings, the practice of using enlistment motives/goals to maximizing enlistment without considering their long-term impact on relationship quality and behavior appears myopic and may fail to maximize long-term value for the military.
Muslim Mothers in Ground Combat Against the Islamic State
Authors: Nilsson Marco
Published: March 2017

This study analyzes the experiences and identities of Kurdish women fighting the Islamic State (IS) in northern Iraq as part of the Peshmerga Army. The case is especially interesting because these women have engaged in ground combat and because there is an empirical gap in knowledge, especially concerning Muslim women’s experiences as soldiers. Wars bring great destruction but can also catalyze social change. While seeking balance between their identities as good mothers and professional soldiers, many Kurdish women see their war participation as a chance to increase their agency and improve equality in society, as combat operations create a window of opportunity to change perceptions of women’s roles. Women soldiers still face prejudices and feel that they must prove their worth as fearless warriors in ground combat. However, interviewed soldiers said that they were not striving for equality but equivalency, stressing those qualities that women in particular can contribute in battle.
Understanding Challenges, Strategies, and the Role of Support Networks in Medication Self-management Among Patients With Type 2 Diabetes
Authors: Bernhard Gerda , Ose Dominik , Baudendistel Ines , Seidling Hanna M. , Stützle Marion , Szecsenyi Joachim , Wensing Michel , Mahler Cornelia
Published: March 2017

Purpose

The purpose of this qualitative study was to investigate the challenges and strategies of patients with type 2 diabetes mellitus (T2DM) regarding daily management of their medication regimen focusing on the role of their support networks.

Methods

A purposeful sample of 25 patients with T2DM was recruited from local self-help groups, general practitioner practices, and a university hospital in southwestern Germany. Four semi-structured focus groups were conducted to identify the challenges patients experienced, the strategies they used, and their collaboration with support networks to assist them in self-managing their medication regimen. Sessions were audio- and video-recorded, fully transcribed, and subjected to computer-aided qualitative content analysis, guided by the Self- and Family Management Framework (SFMF).

Results

Patients with T2DM experienced numerous challenges affecting medication self-management arising from their personal situation, health status and resources, characteristics of their regimen, and how health care is currently organized. Patients’ self-initiated strategies included activating health care, community, social, and online resources; taking ownership of medication-related needs; and integrating medication-taking into daily life. Patients drew on self-help groups, family, and friends to discuss concerns regarding medication safety and receive experience-based information and advice for navigating within the health care system as well as practical hands-on support with daily medication self-management.

Conclusions

Understanding the challenges and building on strategies patients with T2DM devised help diabetes educators to better address patients’ needs and priorities and guide patient-centered interventions to support patients’ self-management activities. Community and social support networks operating in patients’ lives need to be engaged in the self-management support.
Expectations and Attitudes of Individuals With Type 1 Diabetes After Using a Hybrid Closed Loop System
Authors: Iturralde Esti , Tanenbaum Molly L. , Hanes Sarah J. , Suttiratana Sakinah C. , Ambrosino Jodie M. , Ly Trang T. , Maahs David M. , Naranjo Diana , Walders-Abramson Natalie , Weinzimer Stuart A. , Buckingham Bruce A. , Hood Korey K.
Published: March 2017

Purpose

The first hybrid closed loop (HCL) system, which automates insulin delivery but requires user inputs, was approved for treatment of type 1 diabetes (T1D) by the US Food and Drug Administration in September 2016. The purpose of this study was to explore the benefits, expectations, and attitudes of individuals with T1D following a clinical trial of an HCL system.

Methods

Thirty-two individuals with T1D (17 adults, 15 adolescents) participated in focus groups after 4 to 5 days of system use. Content analysis generated themes regarding perceived benefits, hassles, and limitations.

Results

Some participants felt misled by terms such as “closed loop” and “artificial pancreas,” which seemed to imply a more “hands-off” experience. Perceived benefits were improved glycemic control, anticipated reduction of long-term complications, better quality of life, and reduced mental burden of diabetes. Hassles and limitations included unexpected tasks for the user, difficulties wearing the system, concerns about controlling highs, and being reminded of diabetes.

Conclusion

Users are willing to accept some hassles and limitations if they also perceive health and quality-of-life benefits beyond current self-management. It is important for clinicians to provide a balanced view of positives and negatives to help manage expectations.
Loss investigations involving heating element failures: Fire, water, and personal injury
Authors: Green Lee , Shuttlesworth Michael , Buc Elizabeth C
Published: March 2017

Sheathed heating elements, or calrod heaters, are used in a variety of appliances and processes to heat a media (water, air, other fluids). Examples of appliances that utilize sheathed heating elements are water heaters (trough and residential), dishwashers, dry saunas, and RV refrigerator cooling units. The construction and use of various heating elements are reviewed with a focus on design features which may contribute to failures and safety features which should prevent catastrophic failures. This article will expand on NFPA 921 (2014) Section 26.5.7 describing various heating element failures as the root cause of not only fires but also personal injury (e.g. burns, electrocution) and water losses. Common causes and failure modes of heating elements, from case studies and literature, are presented. A basic protocol for the thermal and material characterization and laboratory examination and testing of heating elements and failures is provided.
Characteristics of Effective Classroom Rules: A Review of the Literature
Authors: Alter Peter , Haydon Todd
Published: March 2017

Difficulty managing classroom behavior is a frequently recognized problem for teachers, especially teachers early in their careers. Classroom rules are identified as an integral part of effective classroom management as they are relatively simple to implement and focus on preventing challenging behaviors before they occur. Sources such as classroom management textbooks and practitioner-oriented journal articles recommend a number of characteristics that make classroom rules effective; unfortunately, these sources have not been uniform in their recommendations. The purpose of this review of effective practices is to compare what information teachers are being given either in their preservice coursework or in-service training via textbooks and practitioner-oriented articles with actual empirical research that used classroom rules as an independent variable. Results indicated that the two most important characteristics of effective classroom rules are teaching the rules to students and tying rules to positive and/or negative consequences. Other characteristics recommended in secondary sources remain equivocal in the research. Implications for effective teacher preparation in classroom management are discussed.
Optimal process planning for helical bevel gears using Taguchi design of simulated machining experiments
Authors: Vosniakos George-Christopher , Kalattas Alexandros , Siasos Alexandros
Published: March 2017

Computer-aided manufacturing systems are considered as ‘what-if’ processors, whereby the user suggests manufacturing features and for each one of them a tool and a machining strategy, whereas the system computes tool paths and generates a computer numerical control program. Given the multitude of factors for which decisions are needed, complexity is high. In addition, given the executive nature of computer-aided manufacturing systems, the user relies on experience in exploring parameter value combinations in order to obtain good results. In this work, structured generation of a representative subset of the parameter combination space is advocated using the Taguchi approach. This is applied to parts that are simpler than the average part, since they consist of a single, repeating, yet geometrically complex, machining feature involving sculptured surfaces, such as helical bevel gears. The lack of multiple features reduces the solution space, enabling a manageable number of experiment runs from which good results for roughing and finishing are attained. Statistical processing of these results also point to relative significance of machining strategy parameters within the particular space explored and for the particular weighted criteria employed, that is, rest material, machining time and gouge volume. Excellent results are obtained in this way, based on the machining simulation capabilities of modern computer-aided manufacturing systems and bypassing the inherent lack of intelligence of the latter.
Experimental investigation of porous metal materials in high-speed micro-milling process
Authors: Liu Zhiqiang , Han Jingjing , Su Yu , An QingLong
Published: March 2017

Porous stainless steels, which have recently extended to the microscale domain, have been widely used for biomedical materials because they have good strength-to-weight ratio and superior corrosion resistance. Most components fabricated from porous materials still require secondary machining despite being produced in near-net shapes. However, they have poor machinability. High cutting force, high cutting temperature, poor surface integrity, and severe tool wear are encountered in the machining process of the difficult-to-cut porous materials. This article focuses on the micro-cutting performances and effects of cutting parameters in the micro-milling of porous stainless steel materials, including tool wear patterns and mechanism, effects of tool wear and cutting parameters on surface topography, cutting force, and cutting temperature. Comparative experiments were performed to investigate surface burr and cutting performances of porous materials in the micro-milling process. The effects of machining parameters on porous stainless steels in micro-milling are studied. Furthermore, a preliminary relationship of cutting parameters with micro-milling force and milling temperature is also established. The tool wear patterns and mechanisms were observed. Based on the findings, this article concluded that tool wear influences the surface morphology of the machined part and the effects of structural porosity on the cutting process during the micromachining of porous materials.
Assembly sequence optimization for minimizing the riveting path and overall dimensional error
Authors: Ni Jun , Tang Wen Cheng , Pan Minghui , Qiu Xiaoli , Xing Yan
Published: March 2017

Due to the complexities of calculations based on different representations of constituent parts in an assembly, the combined improvement of efficiency and precision for the riveting has seldom been studied by the sequence planning or dimensional engineering. This article develops an assembly sequence optimization method that simultaneously minimizes the path length and overall dimensional error for the solid riveting. The sequence is denoted by the order of classifications for the nodes around the rivet holes in the finite element model for the assembly. Ant colony algorithm is applied on the optimization by integrating two calculations, that is, the length calculation of riveting path and the calculation of the dimensional error related to rivet upsetting directions and assembly sequence. Results for three assemblies are presented which show a good degree of optimization in performance for different scales of assemblies with different numbers of rivets that share the same solid riveting process.
A two-stage novel approach using centre ordering of vectors on agglomerative hierarchical clustering for manufacturing cell formation
Authors: Bera Samiran , Chattopadhyay Manojit , Dan Pranab K
Published: March 2017

Cellular manufacturing is a prevailing pursuit in increasing productivity and throughput and in reducing setup and lead time in production systems that are configured as clusters of machines or facilities. Although several approaches exist today to optimize the quality of cluster, they are cumbersome in terms of implementation due to high complexity and resource requirements. In this work, these issues are addressed effectively using a novel two-stage approach which integrates centre ordering of vectors on ring and an agglomerative hierarchical clustering. The centre ordering of vectors on ring–agglomerative hierarchical clustering approach is much simpler and quicker to grasp and implement in a resource-constraint environment. Problem sets retrieved from the existing literature are put to experimentation for optimality and are compared to study improvements using grouping efficacy. The proposed method has yielded significant improvement, as found from the experimental results, over earlier reported ones. This establishes the centre ordering of vectors on ring–agglomerative hierarchical clustering algorithm as an efficient approach for clustering. Furthermore, the number of iterations required to reach optimality is significantly lesser, compared to the ones obtained through existing approaches based on mathematical models and heuristics.
A new paradigm for virtual knowledge sharing in product development based on emergent social software platforms
Authors: Evans Richard David , Gao James Xiaoyu , Martin Nick , Simmonds Clive
Published: March 2017

The UK Government considers its Aerospace Industry a remarkable success story, enjoying a global market share of 17% in 2015. The capture, management and sharing of employee knowledge is seen as vital if the industry is to remain highly innovative and retain its pre-eminent position internationally. Aerospace manufacturers, such as BAE Systems, often have to re-engineer business processes routinely to ensure their survival. Knowledge sharing in the industry is seen as challenging due to the dispersed nature of its operations and multi-tier supply chains. This article, through a 5-year participant-observation study at the World’s second largest aerospace and defence organisation, BAE Systems, proposes a new paradigm for virtual knowledge sharing in dispersed aerospace product development based on emergent social software platforms such as Enterprise 2.0 technologies. The developed framework and methodologies are applied to the bespoke BAE Systems’ engineering lifecycle process to validate its effectiveness with results indicating that Enterprise 2.0 technologies offer a more openly innovative environment in which employees may share and interact with knowledge more effectively and easily across geographical and functional boundaries, compared with conventional engineering information systems.
The influence of malalignment and ageing following sterilisation by gamma irradiation in an inert atmosphere on the wear of ultra-high-molecular-weight polyethylene in patellofemoral replacements
Authors: Maiti Raman , Cowie Raelene M , Fisher John , Jennings Louise M
Published: March 2017

Complications of patellofemoral arthroplasty often occur soon after implantation and, as well as other factors, can be due to the design of the implant or its surgical positioning. A number of studies have previously considered the wear of ultra-high-molecular-weight polyethylene patellae following suboptimal implantation; however, studies have primarily been carried out under a limited number of degrees of freedom. The aim of this study was to develop a protocol to assess the wear of patellae under a malaligned condition in a six-axis patellofemoral joint simulator. The malalignment protocol hindered the tracking of the patella centrally in the trochlear groove and imparted a constant 5° external rotation (tilt) on the patella button. Following 3 million cycles of wear simulation, this condition had no influence on the wear of ultra-high-molecular-weight polyethylene patellae aged for 4 years compared to well-positioned non-aged implants (p > 0.05). However, under the malaligned condition, ultra-high-molecular-weight polyethylene patellae aged 8–10 years after unpacking (following sterilisation by gamma irradiation in an inert atmosphere) and worn ultra-high-molecular-weight polyethylene components also aged 4 years after unpacking (following the same sterilisation process) exhibited a high rate of wear. Fatigue failure due to elevated contact stress led to delamination of the ultra-high-molecular-weight polyethylene and in some cases complete failure of the patellae. The results suggest that suboptimal tracking of the patella in the trochlear groove and tilt of the patella button could have a significant effect on the wear of ultra-high-molecular-weight polyethylene and could lead to implant failure.
A comparison between electromechanical and pneumatic-controlled knee simulators for the investigation of wear of total knee replacements
Authors: Abdelgaied Abdellatif , Fisher John , Jennings Louise M
Published: March 2017

More robust preclinical experimental wear simulation methods are required in order to simulate a wider range of activities, observed in different patient populations such as younger more active patients, as well as to fully meet and be capable of going well beyond the existing requirements of the relevant international standards. A new six-station electromechanically driven simulator (Simulation Solutions, UK) with five fully independently controlled axes of articulation for each station, capable of replicating deep knee bending as well as other adverse conditions, which can be operated in either force or displacement control with improved input kinematic following, has been developed to meet these requirements. This study investigated the wear of a fixed-bearing total knee replacement using this electromechanically driven fully independent knee simulator and compared it to previous data from a predominantly pneumatically controlled simulator in which each station was not fully independently controlled. In addition, the kinematic performance and the repeatability of the simulators have been investigated and compared to the international standard requirements. The wear rates from the electromechanical and pneumatic knee simulators were not significantly different, with wear rates of 2.6 ± 0.9 and 2.7 ± 0.9 mm3/million cycles (MC; mean ± 95% confidence interval, p = 0.99) and 5.4 ± 1.4 and 6.7 ± 1.5 mm3/MC (mean ± 95 confidence interval, p = 0.54) from the electromechanical and pneumatic simulators under intermediate levels (maximum 5 mm) and high levels (maximum 10 mm) of anterior–posterior displacements, respectively. However, the output kinematic profiles of the control system, which drive the motion of the simulator, followed the input kinematic profiles more closely on the electromechanical simulator than the pneumatic simulator. In addition, the electromechanical simulator was capable of following kinematic and loading input cycles within the tolerances of the international standard requirements (ISO 14243-3). The new-generation electromechanical knee simulator with fully independent control has the potential to be used for a much wider range of kinematic conditions, including high-flexion and other severe conditions, due to its improved capability and performance in comparison to the previously used pneumatic-controlled simulators.
Circle (CO2 reabsorbing) breathing systems: Human applications
Authors: Magee Patrick
Published: March 2017

Artificial breathing systems to help humans survive extreme environments are used over a range of ambient pressures, using various gases of different volumetric concentrations. These activities include anaesthesia and intensive care activity, high-altitude mountaineering, firefighting, aerospace extravehicular space activity and underwater diving operations. A circle breathing system is one in which the exhaled carbon dioxide is absorbed by an alkali substance and the remaining unused gases are recirculated, usually for the sake of economy and environment. This allows the flow of the fresh gas to be considerably reduced, thereby saving on fresh-gas supply. Circle systems are often used in the circumstances cited above, although not always at low fresh-gas flows. The circle system used in anaesthesia and intensive care has the least engineering demands made on it, although it is used on patients who are highly vulnerable; it usually provides a mixture of air and oxygen, and perhaps a breathable anaesthetic gas, all at sea-level pressure. Mountaineering and firefighting applications involve an extreme earthbound environment, with the user undergoing extreme physical work. The astronaut’s spacesuit and life support system contains a high-flow circle system, the breathing gases themselves pressurising the suit as well as providing respiratory life support and thermal comfort; the gas provided is pure oxygen at about a third of sea-level atmosphere. There are numerous varieties of breathing systems for diving, including a circle system, often for clandestine naval activity; the gases used are a combination of oxygen, nitrogen and helium, to minimise the possibility of decompression sickness, nitrogen narcosis and oxygen toxicity and must be provided at a varying pressure and concentration appropriate to depth.
Impact of Using Conventional Inlet/Outlet Boundary Conditions on Haemodynamic Metrics in a Subject-Specific Rabbit Aorta
Authors: McElroy Michael , Keshmiri Amir
Published: March 2017

Computational fluid dynamics is a tool capable of accurately measuring metrics currently used to predict the behaviour of cardiovascular diseases. This study quantifies the impact various commonly used inlet and outlet boundary conditions have on various shear rate–based haemodynamic metrics currently used for predicting the localisation of cardiovascular diseases. Simulations are conducted on an accurately represented rabbit aorta configuration and comparison has been made against available in vivo data. The boundary conditions studied include two different inlet profiles, three outlet boundary conditions, and steady-state versus pulsatile flow cases. Large variations were found in the results, particularly when using different outlet boundary conditions, and the discrepancies were evaluated both quantitatively and qualitatively. The results clearly highlight the importance of the type of boundary condition used when simulating complex cardiovascular models. By restricting the attention to the flow within the aorta and the intercostal branches, the results suggest that prescribing transient simulation and fully developed flow at the inlet are not required. Furthermore, assuming the widely accepted low wall shear stress theory of Caro, it was found that Murray’s law–based outlet boundary condition returns the most physiologically accurate results when compared to in vivo data.
Embedded piezoelectric lead-zirconate-titanate-based dynamic internal normal stress sensor for concrete under impact
Authors: Xu Bin , Song Gangbing , Mo YL
Published: March 2017

The direct stress measurement is critical for the constitutive law investigation of concrete materials and dynamic behavior study of concrete structures under strong dynamic loadings where the strain-rate effect and the plastic behavior should be considered. In this article, an embedded dynamic internal normal stress sensor for concrete by employing piezoelectric lead-zirconate-titanate (PZT) patch as a sensing element is developed. After being calibrated under sinusoidal loadings with different frequencies, periodical square loadings, and random loadings, the developed dynamic internal normal stress sensor is further calibrated with a unique self-developed free-falling drop hammer with different impact velocities. The sensitivity of the developed normal stress sensor is determined accordingly. Finally, the developed sensors are employed to monitor the dynamic normal stress time history at different locations of concrete cylinder specimens under impacts with different velocities using a large-scale drop hammer test facility. The dynamic increase factors of concrete strength under impact are determined and compared with the values determined by the Comité Euro-International du Béton code. The experimental results indicate that the PZT-based embedded dynamic internal normal stress sensor provides a novel way for the direct dynamic normal stress measurement of concrete specimens under impact loadings.
Rising Cost of Anticancer Medications in the United States
Authors: Jackson Kristy , Nahata Milap C.
Published: March 2017

With more than 1.6 million new cases of cancer occurring each year, anticancer medications are in high demand. Escalating prescription drug prices have become a significant concern. Anticancer medications are among the most expensive prescription medications, many of them exceeding $100 000 a year. The survival benefits of certain newer anticancer medications may be a few months more than that from the existing treatment but at a much higher price tag. Drug cost may play a substantial role in making treatment choices. Multiple factors leading to high prices and some potential solutions to lower them have been highlighted.