bluuebunny/crossref_metadata_2025 huggingface dataset:
Train-to-Train Impact Test: Occupant Protection Experiments
Authors: Tyrell David , Zolock John , VanIngen-Dunn Caroline
Published: June 2008

This paper describes the results of the occupant protection experiments included as part of the train-to-train impact test conducted at the Transportation Technology Center in Pueblo, Colorado on January 31, 2002. In this test, a cab car-led train, initially moving at 30 mph, collided with a standing locomotive-led train. The initially moving train included a cab car, three coach cars, and a trailing locomotive, while the initially standing train included a locomotive and two open-top hopper cars. The hopper cars were ballasted with earth such that the two trains weighed the same, approximately 635 kips each. The cars were instrumented with strain gauges, accelerometers, and string potentiometers, to measure the deformation of critical structural elements, the longitudinal, vertical, and lateral car body accelerations, and the displacements of the truck suspensions. As part of the test, the cars were equipped with instrumented test dummies seated in three interior arrangements: 1. Forward-facing unrestrained occupants seated in rows, compartmentalized by the forward seat in order to limit the motions of the occupants. 2. Forward-facing restrained occupants with lap and shoulder belts. 3. Forward-facing unrestrained occupant seated in the locomotive operator seat. The longitudinal, vertical, and lateral motions of the cars during the train-to-train impact test are discussed in the paper, as well as their influence on the responses of the instrumented dummies. The lateral motions of the cars had some influence on the response of the test dummies, however the vertical motions of the cars had a greater influence on their response. During the test, the cab car overrode the locomotive. This large upward vertical motion of the cab car helped the test dummies in the cab car remain in their seats. The longitudinal motions of the cars during the train-to-train test had lower injury potential than the longitudinal motions of the cars in the previously conducted single- and two-car impact tests. (In these tests, a single car impacted a fixed barrier and two coupled cars impacted a fixed barrier, respectively. Test dummies were also included in both of these tests.) In the train-to-train test the test dummies endured a much longer crash pulse, with a lower average longitudinal acceleration than in the single-car and two-car impact tests. In the train-to-train test only one unrestrained test dummy landed in the aisle after impacting the seat in front of it. All injury criteria values remained below threshold values.
Evolution of Ground Level Scalar Concentrations Through a Compact Cylinder Array Embedded in the Atmospheric Surface Layer
Authors: Miner Heidi E. , Rasmussen Adam
Published: June 2008

Experiments for this study were designed to understand gas dispersion in the presence of surface mounted obstacles. To this end, model field experiments were conducted in a compact barrel array employing a spatial distribution of concentration sensors. Specific aims were to explore the effects of atmospheric stability and plume source initial conditions on the plume dispersion through the barrel array. The present results indicate a relaxation towards Gaussian behavior along the plume centerline. The rate of this Gaussian-like behavior is dependent upon atmospheric stability conditions. Plume dispersion through the array appears to be independent of source initial conditions under neutrally stable conditions.
The Use of Wind Tunnel, Field, and Computational Studies to Determine Building Wake Effects on the Hill Air Force Base Runway
Authors: Arnim Nathan M. , Wall Trent L. , Waterhouse Jeff
Published: June 2008

A combined wind tunnel, field measurement, and numerical simulation strategy was used to obtain estimates of the effects of canyon wind flow over proposed building arrays on the Hill Air Force Base (HAFB) runway. As part of this effort, simplified building configurations in the wind tunnel were utilized to optimize computation parameters, as well as gain insights regarding the gross features associated with the proposed building configurations. The field data were used to provide realistic inflow conditions to the numerical simulations. The simulations were then utilized to predict flow fields over the HAFB runway for a number of proposed building configurations. Results from the study, indicated that building configurations primarily oriented transverse to the flow direction showed a persistence of momentum deficit and increased turbulence at large downstream distances. The present solution strategy is shown to constitute a cost effective means of addressing complex applied wind engineering problems with the capability of overcoming Reynolds number and geometric similarity problems.
Interface Strength Between Sub-Micron Thin Films in Opening and Sliding Delamination Modes
Authors: Shibutani Tadahiro , Tsuruga Tetsu , Yu Qiang , Shiratori Masaki
Published: June 2008

Delamination between thin films is classified into two types: opening mode and sliding mode. Corresponding to each mode, there is the interface strength between thin films. This paper aims to evaluate interface strength between the sub-micron thin films for opening mode and sliding mode, respectively. We already developed the evaluation method of interface fracture toughness for opening mode on the basis of fracture mechanics concept elsewhere. Moreover, the evaluation method of sliding mode is proposed and the interface strength between thin films for an advanced LSI is evaluated as the fracture toughness by using both methods. In both modes, the stress singularity appears in the vicinity of the edge of interface and governs the delamination. The criterion of crack initiation for each mode is evaluated as the interface toughness. The fracture toughness at the edge of interface in sliding mode is lower than that in opening mode.
Improved Analytical and Semi-Analytical Durability Models (Constrained Models) for Various Surface-Mount Configurations
Authors: Sharma Pradeep , Loman James
Published: June 2008

Several analytical and semi-analytical models to predict solder joint durability under thermal cycling loadings have been proposed. In general, these models are overtly conservative often requiring extensive experimental and/or finite element calibration. We present, based on the physics of the deformation process, a direct approach to improve these classes of model by resolving one of the major causes of conservatism. Our contribution is applicable to virtually all known surface mount configurations. The improved models (henceforth termed as constraint models) retain the simplicity of use of the existing ones. The efficacy of constraint approach is demonstrated on leadless resistors and comparisons are made with existing models and experimental data.
Modified Decohesion Test (MDT) for Interfacial Fracture Toughness Measurement in Microelectronic/MEMS Applications
Authors: Modi Mitul B. , Sitaraman Suresh K.
Published: June 2008

Delamination of intrinsically or residually stressed thin films is commonly encountered in microelectronics and MEMS systems. Thin films typically accrue stresses through micro structural variations caused by physical vapor deposition, thermally induced stresses imposed due to thermal mismatch, and/or extrinsically introduced forces. These stresses can reach upwards of 1 GPa and can easily exceed the strength of the metal thin film interface. Knowledge of the interfacial fracture toughness (Γ) is necessary to predict if delamination will occur. However, measuring Γ is a challenge for thin film interfaces. Typical testing methods such as bimaterial cantilever, microscratch, peel, bulge, or edge lift-off are limited to organic films, cause complex stress fields, can only measure a single mode mix, or cannot achieve the large energy release rates typical of metal thin film interfaces. A new approach based on the decohesion test, called the modified decohesion test (MDT), eliminates these shortcomings of current testing methods. In this approach, a highly stressed super layer is used to drive delamination and “tune-in” the mode mix at the crack tip. Since the deformations remain elastic, a mechanics-based solution can be used to correlate test parameters to the energy release rate. Common IC fabrication techniques are used to prepare the sample and execute the test, thereby making the test compatible with current microelectronic or MEMS facilities. Varying the crack surface area rather than the energy in the super layer allows the ability to bound Γ using a single test wafer providing a 90% savings in resources and 95% savings in time. Other modifications allow application of the method to highly chemically reactive metals and decrease the sample preparation time. Design, preparation, and execution of the MDT are presented. Results of finite element models are used to validate the approach. Results are shown for a Ti/Al2O3 interface.
A Full-Scale 3D Finite Element Analysis for No-Underfill Flip Chip Package
Authors: Hsu S. M. , Lin J. C. , Chiang K. N.
Published: June 2008

This research establishes a micro-macro 3D finite element model for no underfill flip chip BGA package. The no underfill package uses a ceramic-like (CTE close to silicon) material mounted on the backside of the flip chip substrate to constrain the thermal expansion of the organic substrate and enhance the reliability of the solder joint. This work attempts to design a constrained structure to enhance the reliability of the no underfill flip chip package. For the special design of constrained structure, a full-scale 3D finite element model is needed to investigate some mechanical behaviors that cannot be revealed by the 2D finite element model. However, to establish a full-scale 3D finite element model, the large computation time is an issue. The equivalent beam concept is adopted in this research to overcome this drawback of the finite element models. The results indicate that the equivalent beam concept is a feasible methodology for reducing the computation time of the 3D finite element model. Further, the new design structure could improve package reliability, increase manufacturing throughput and thermal performance, and maintain reworkability of the flip chip structure.
Process-Induced Stress Effect on Reliability of ChipSeal® Passivation Technology
Authors: Kim Yeong K. , Krondorfer Rudolf , Sitaraman Suresh K.
Published: June 2008

It is important to take into consideration the process-induced residual stress into reliability prediction modeling. Lack of process-induced stress may lead to error in reliability prediction. Therefore, careful investigation of the stress development is critical. In this paper, the stress development induced by ChipSeal® passivation process technology has been analyzed. The ChipSeal® passivation technology has been developed to enhance the reliability of commercially-off-the-shelf plastic encaptulated microelectronics component by sealing integrated circuit at the wafer level. The analysis takes every process step into account to investigate the temperature effect on the final residual stress. The section of the fabricated structure has been modeled in two different configurations. The stress developments have been simulated by numerical method, and the results have been analyzed to identify the critical location. Three different lengths of metal layer have been considered to investigate the effect of metal layer length structure. Finally, a response surface method is employed to determine the thickness effect of individual layers and to develop design guidelines to enhance ChipSeal® reliability.
Reliability Evaluation of CSP Using New Flip-Chip Bonding Technology: Both-Sided CSP and Single-Sided CSP
Authors: Koguchi Hideo , Taweejun Nipon , Nishida Kazuto , Sasaki Chie
Published: June 2008

Chip-size packaging (CSP) attracts largely attentions due to its lighter, thinner and smaller size. In this study, the deformations and the stresses in the CSP fabricated by non-conductive film stud-bump direct interconnection (NSD) were analyzed. The reliability evaluation of single-sided CSP and both-sided CSP were investigated for heat cycles. The material parameters, i.e. stresses, strains and deformations, for achieving a high reliability of CSP were investigated using a finite element method and experiment. The dependency of the life in single-sided CSP and both-sided CSP on the thicknesses of IC and substrate could be expressed using a normal stress in the thickness direction and shear stress in the vertical cross section, respectively.
Gold to Gold Thermosonic Flip Chip Bonding on Ceramic Substrate
Authors: Wei J. , Wang Z. P. , Tan Y. M.
Published: June 2008

In this study, a thermosonic flip chip process has been developed to assemble gold bumped die to an Al2O3 ceramic substrate. The effects of bonding conditions, such as ultrasonic power, temperature, bonding force and bonding time, on the reliability of the interconnections were investigated. It was found that ultrasonic power and bonding force were the major factors influencing the reliability. High ultrasonic power and bonding force resulted in high reliability. The thermal cycling test results (from −55 °C to 125 °C) showed that the assemblies passed 1250 cycles with no change in resistance. The pressure cooker test results (15 psig pressure and 100% RH at temperature of 121 °C) showed that the assemblies passed 168 hours with no change in resistance. The shear force test results showed that the shear force at failure ranged from 10 to 40 grams per bump depending on bonding parameters. The interconnect cross-sections and the fracture surfaces on selected dies and substrates were observed with scanning electron microscope (SEM). It was found that the shear failure usually occurred between a gold pad and ceramic substrate, indicating a strong bonding interface between the gold bump and pad on the substrate. The performance of the assemblies fell into the reliable region as long as the bonding force, temperature, and ultrasonic power were high enough. The failure mechanisms consisted of separation between Au bump and Au pad, separation between Au pad and substrate and cracking inside Au pad or trace. The ultrasonic power drove relative movement between Au bumps and Au pads, causing friction and heat in the interface to result in micro-welding.
High-Lead Solder Ball Characteristics in BGA Package
Authors: Kao Nicholas , Wang Y. P. , Hsiao C. S.
Published: June 2008

For high performance packages in mainframe systems such as networking switch, telecommunication equipments, higher reliability is always required. Using high-lead solder ball is an effective way to enhance the solder joint performance in board level. The elongation property of high-lead alloy Sn10/Pb90 is 10 times greater than eutectic Sn/Pb alloy. The high-lead ball has higher melting temperature, it can maintain the stand off (gap) between the package and PCB when eutectic solder paste melted at 220°C. In this study, the performances of high-lead solder Sn10/Pb90 and eutectic Sn63/Pb37 are compared. A series of experiments are performed to characterize the high-lead solder ball solder joint performance. The ball shear test parameters also affect high-lead solder ball strength, such as ram height and shear speed. Lower ram height and higher speed increases the ball shear strength value. Effect of different ball pad openings, solder paste volume and reflow profile for ball placement, is also discussed in this paper. the ratio of ball pad opening diameter to solder ball diameter is related to ball shear force. When the ratio is 0.83, the ball shear is better than other value. The most important factor to ball shear strength is the solder paste amount. However, the reflow condition (the time period over 183°C) isn’t the significant factor to affect the ball shear strength.
What are the breast support choices of Australian women during physical activity?
Authors: Bowles K-A , Steele J R , Munro B
Published: June 2008

Objectives:

This study aimed to quantify the breast support wearing and purchasing habits of young women and to assess factors that affect their sports bra usage during physical activity.

Design:

Study results were obtained from a self-administered mail survey, which was posted to participants after gaining their verbal consent via random telephone recruitment.

Participants:

413 women aged 20 to 35 years were recruited from New South Wales, Australia.

Results:

From the returned (65%) surveys only 41% of respondents currently wore an encapsulating sports bra during physical activity, primarily due to a lack of awareness of the importance of good breast support during physical activity. Bra size was a predictor of sports bra usage, whereby participants with large breasts were more than twice as likely to wear a sports bra as their smaller-breasted counterparts.

Conclusions:

It was concluded that, although encapsulating sports bras have been shown to effectively reduce breast motion and associated exercise-induced breast discomfort, these bras were not the breast support option most commonly chosen by young women during physical activity. It is recommended that all women, irrespective of breast size, be educated on the importance of wearing a well-fitted and supportive bra during physical activity to decrease excessive strain on breast tissue structures and related breast discomfort.
Parachuting from fixed objects: descriptive study of 106 fatal events in BASE jumping 1981–2006
Authors: Westman A , Rosén M , Berggren P , Björnstig U
Published: June 2008

Objective:

To analyse the characteristics of fatal incidents in fixed object sport parachuting (building, antenna, span, earth (BASE) jumping) and create a basis for prevention.

Design:

Descriptive epidemiological study.

Participants:

Data on reported fatal injury events (n = 106) worldwide in 1981–2006 retrieved from the BASE fatality list.

Assessment of risk factors:

Human, equipment and environmental factors.

Main outcome measurements:

Identification of typical fatal incident and injury mechanisms for each of the four fixed object types of BASE jumping (building, antenna, span, earth).

Results:

Human factors included parachutist free fall instability (loss of body control before parachute deployment), free fall acrobatics and deployment failure by the parachutist. Equipment factors included pilot chute malfunction and parachute malfunction. In cliff jumping (BASE object type E), parachute opening towards the object jumped was the most frequent equipment factor. Environmental factors included poor visibility, strong or turbulent winds, cold and water. The overall annual fatality risk for all object types during the year 2002 was estimated at about one fatality per 60 participants.

Conclusions:

Participants in BASE jumping should target risk factors with training and technical interventions. The mechanisms described in this study should be used by rescue units to improve the management of incidents.
A delayed bone–tendon junction healing model established for potential treatment of related sports injuries
Authors: Wang L , Qin L , Cheung W-H , Lu H-B , Yang X-H , Leung K-S , Wong M W-N , Chan K-M
Published: June 2008

Background

Animal models for the study of tendinopathy and bone–tendon (B–T) junction repair have been established in the past for sports medicine research. As healing at the B–T junction is difficult and sometimes delayed, establishing a delayed B–T healing experimental model is therefore essential to study the efficacy of potential biophysical and biological interventions for treatment of B–T junction healing.

Objective

To test the hypothesis that a delay in B–T healing could be modelled by shielding the B–T healing interface for the initial few weeks.

Methods

Using an established partial patellectomy model in rabbits, the B–T healing interface was shielded with a latex slice for the first 4 postoperative weeks in mature female rabbits. The characteristics of delay in B–T repair (n = 10) compared with controls (n = 10) were evaluated at 8 and 12 postoperative weeks.

Results

Radiology showed consistent delay in osteogenesis at the healing interface in all samples in the delayed healing group; growth of new bone was only 25.8% and 50.1% of that in the control group at weeks 8 and 12, respectively. Bone mineral density was 56.0% lower in the delayed healing group at week 8, but this difference diminished at week 12. The quality of B–T healing was poor in the delayed healing group, with 22.9% and 24.2% lower failure load than the control group at weeks 8 and 12, respectively. The healing quality was also reflected by histological findings.

Conclusions

A delayed B–T healing experimental model was established for the first time for future sports medicine research.
Screening the athlete’s shoulder for impingement symptoms: a clinical reasoning algorithm for early detection of shoulder pathology
Authors: Cools A M , Cambier D , Witvrouw E E
Published: June 2008

Chronic shoulder pain and dysfunction are common complaints among overhead athletes seeking care from physical medicine and rehabilitation. Impingement is a frequently described pathological condition in the overhead athlete. Impingement symptoms may be the result of rotator cuff pathology, shoulder instability, scapular dyskinesis or muscle dysfunction, biceps pathology, SLAP lesions and chronic stiffness of the posterior capsule. At present, numerous different shoulder tests have been described in literature and discussed with respect to their individual diagnostic accuracy. However, in view of the number of shoulder tests, it is often a challenge for the clinician to select the appropriate tests for diagnosing the underlying pathology. The purpose of this paper is to present and discuss a clinical algorithm which may be used in the early detection of the underlying causes of impingement symptoms. In this algorithm, a specific chronology and selection of diagnostic tests may offer the clinician a guideline in his physical examination of the athlete with shoulder pain.
Induction of stearoyl-CoA desaturase protects human arterial endothelial cells against lipotoxicity
Authors: Peter Andreas , Weigert Cora , Staiger Harald , Rittig Kilian , Cegan Alexander , Lutz Philipp , Machicao Fausto , Häring Hans-Ulrich , Schleicher Erwin
Published: June 2008

Endothelial lipotoxicity has been implicated in the pathogenesis of multiple stages of cardiovascular disease from early endothelial dysfunction to manifest atherosclerosis and its complications. Saturated free fatty acids are the major inducers of endothelial cell apoptosis and inflammatory cytokines. In humans, the enzyme human stearoyl-CoA desaturase-1 (hSCD-1) is the limiting step of the desaturation of saturated to monounsaturated fatty acids. Since we could demonstrate the expression of SCD-1 in primary human arterial endothelial cells (HAECs), we aimed to prove a beneficial role of upregulated hSCD-1 expression. In contrast to other cells that are less susceptible to lipotoxicity, hSCD-1 was not upregulated in HAECs upon palmitate treatment. Following that, we could show that upregulation of hSCD-1 using the LXR activator TO-901317 in HAECs protects the cells against palmitate-induced lipotoxicity, cell apoptosis, and expression of inflammatory cytokines IL-6 and IL-8. Increased hSCD-1 activity was determined as increased C16:1/16:0 ratio and enhanced triglyceride storage in palmitate treated cells. The beneficial effect was clearly attributed to enhanced hSCD-1 activity. Overexpression of hSCD-1 blocked palmitate-induced cytotoxicity, and knockdown of hSCD-1 using siRNA abolished the protective effect of TO-901317 in HEK-293 cells. Additionally, inhibition of hSCD-1 with 10/12 CLA blocked the effect of TO-901317 on palmitate-induced lipotoxicity, cell apoptosis, and inflammatory cytokine induction in HAECs. We conclude that upregulation of hSCD-1 leads to a desaturation of saturated fatty acids and facilitates their esterification and storage, thereby preventing downstream effects of lipotoxicity in HAECs. These findings add a novel aspect to the atheroprotective actions of LXR activators in cardiovascular disease.
Cardioselective dominant-negative thyroid hormone receptor (Δ337T) modulates myocardial metabolism and contractile efficiency
Authors: Hyyti Outi M. , Olson Aaron K. , Ge Ming , Ning Xue-Han , Buroker Norman E. , Chung Youngran , Jue Thomas , Portman Michael A.
Published: June 2008

Dominant-negative thyroid hormone receptors (TRs) show elevated expression relative to ligand-binding TRs during cardiac hypertrophy. We tested the hypothesis that overexpression of a dominant-negative TR alters cardiac metabolism and contractile efficiency (CE). We used mice expressing the cardioselective dominant-negative TRβ1mutation Δ337T. Isolated working Δ337T hearts and nontransgenic control (Con) hearts were perfused with13C-labeled free fatty acids (FFA), acetoacetate (ACAC), lactate, and glucose at physiological concentrations for 30 min.13C NMR spectroscopy and isotopomer analyses were used to determine substrate flux and fractional contributions (Fc) of acetyl-CoA to the citric acid cycle (CAC). Δ337T hearts exhibited rate depression but higher developed pressure and CE, defined as work per oxygen consumption (MV̇o2). Unlabeled substrate Fc from endogenous sources was higher in Δ337T, but ACAC Fc was lower. Fluxes through CAC, lactate, ACAC, and FFA were reduced in Δ337T. CE and Fc differences were reversed by pacing Δ337T to Con rates, accompanied by an increase in FFA Fc. Δ337T hearts lacked the ability to increase MV̇o2. Decreases in protein expression for glucose transporter-4 and hexokinase-2 and increases in pyruvate dehydrogenase kinase-2 and -4 suggest that these hearts are unable to increase carbohydrate oxidation in response to stress. These data show that Δ337T alters the metabolic phenotype in murine heart by reducing substrate flux for multiple pathways. Some of these changes are heart rate dependent, indicating that the substrate shift may represent an accommodation to altered contractile protein kinetics, which can be disrupted by pacing stress.
Gustatory Neural Circuitry in the Hamster Brain Stem
Authors: Cho Young K. , Li Cheng-Shu
Published: June 2008

The nucleus of the solitary tract (NST) and the parabrachial nuclei (PbN) are the first and second central relays for the taste pathway, respectively. Taste neurons in the NST project to the PbN, which further transmits taste information to the rostral taste centers. Nevertheless, details of the neural connections among the brain stem gustatory nuclei are obscure. Here, we investigated these relationships in the hamster brain stem. Three electrode assemblies were used to record the activity of taste neurons extracellularly and then to electrically stimulate these same areas in the order: left PbN, right PbN, and right NST. A fourth electrode, a glass micropipette, was used to record from gustatory cells in the left NST. Results showed extensive bilateral communication between brain stem nuclei at the same level: 1) 10% of 96 NST neurons projected to the contralateral NST and 58% received synaptic input from the contralateral NST; and 2) 12% of 43 PbN neurons projected to the contralateral PbN and 21% received synaptic input from the contralateral PbN. Results also showed extensive communication between levels: 1) as expected, the majority of 119 NST neurons, 82%, projected to the ipsilateral PbN, but 85% of the 20 NST neurons tested received synaptic input from the ipsilateral PbN, as did 59% of 22 NST neurons that did not project to the PbN; and 2) although few, 3%, of 119 NST cells projected to the contralateral PbN and 38% received synaptic input from the contralateral PbN. These results demonstrated that taste neurons in the NST not only project to, but also receive descending input from the bilateral PbN and that gustatory neurons in the NST and PbN also communicate with the corresponding nucleus on the contralateral side.
Disruption of Balanced Cortical Excitation and Inhibition by Acoustic Trauma
Authors: Scholl Ben , Wehr Michael
Published: June 2008

Sensory deafferentation results in rapid shifts in the receptive fields of cortical neurons, but the synaptic mechanisms underlying these changes remain unknown. The rapidity of these shifts has led to the suggestion that subthreshold inputs may be unmasked by a selective loss of inhibition. To study this, we used in vivo whole cell recordings to directly measure tone-evoked excitatory and inhibitory synaptic inputs in auditory cortical neurons before and after acoustic trauma. Here we report that acute acoustic trauma disrupted the balance of excitation and inhibition by selectively increasing and reducing the strength of inhibition at different positions within the receptive field. Inhibition was abolished for frequencies far below the trauma-tone frequency but was markedly enhanced near the edges of the region of elevated peripheral threshold. These changes occurred for relatively high-level tones. These changes in inhibition led to an expansion of receptive fields but not by a simple unmasking process. Rather, membrane potential responses were delayed and prolonged throughout the receptive field by distinct interactions between synaptic excitation and inhibition. Far below the trauma-tone frequency, decreased inhibition combined with prolonged excitation led to increased responses. Near the edges of the region of elevated peripheral threshold, increased inhibition served to delay rather than abolish responses, which were driven by prolonged excitation. These results show that the rapid receptive field shifts caused by acoustic trauma are caused by distinct mechanisms at different positions within the receptive field, which depend on differential disruption of excitation and inhibition.
A Descriptive Study of Non-Cystic Fibrosis Bronchiectasis in a Pediatric Population from Central and Southern Italy
Authors: Santamaria Francesca , Montella Silvia , Pifferi Massimo , Ragazzo Vincenzo , De Stefano Sara , De Paulis Nicoletta , Maglione Marco , Boner Attilio L.
Published: June 2008

Background: Non-cystic fibrosis (CF) bronchiectasis is now identified more often than in the past. Objectives: It was the aim of this study to assess the high-resolution computed tomography (HRCT) localization and extent of bronchiectasis and to determine whether asthma status, atopy and bronchiectasis distribution are associated with the etiology of bronchiectasis. Methods: We retrospectively analyzed clinical, laboratory, functional and HRCT data of 105 children with non-CF bronchiectasis at 2 tertiary respiratory units in Italy. Forty cases had bronchiectasis associated with ongoing underlying conditions, namely primary ciliary dyskinesia, primary immunodeficiency or aspiration. Results: Age at the onset of chronic cough/wheeze and at the first X-ray-documented pneumonia as well as atopy prevalence were lower in patients with ongoing underlying conditions than in those without (p = 0.049, p = 0.003 and p = 0.0008, respectively). In most cases, bronchiectasis was multilobar, and a mean of 2.5 lobes were involved. The right side was more often involved than the left (88 vs. 70%; p = 0.002), and the upper lobes were relatively spared (p < 0.000001). Right lung involvement and multilobar disease were more prevalent in children younger than 2 years at first pneumonia (p < 0.05). Conclusions: Clinical information combined with laboratory data provides additional insights into the characteristics of non-CF bronchiectasis in a large population of Italian children. This study highlights the need for longitudinal evaluations, also using HRCT, of severe and non-resolving pneumonia in children.
Effects of Sex, Gender Role Identification, and Gender Relevance of Two Types of Stressors on Cardiovascular and Subjective Responses
Authors: van Well Sonja , Kolk Annemarie M. , Klugkist Irene G.
Published: June 2008

The authors tested the hypothesis that a match between the gender relevance of a stressor and one's sex or gender role identification would elicit higher cardiovascular responses. Healthy female and male undergraduates ( n = 108) were exposed to two stressors: the Cold Pressor Test (CPT) and the n-back task. Stressor relevance was manipulated to be masculine or feminine relevant or gender neutral. Data were analyzed using a Bayesian model selection procedure. The results showed stronger cardiovascular responses for the CPT in the case of a gender match effect. In contrast, results for the n-back task revealed stronger cardiovascular responses for sex and gender mismatch effects. These discrepant match and mismatch effects are discussed in terms of differential task appraisal (i.e., threat vs. challenge). Additional results (a) support the success of measuring gender role identification indirectly by means of the Gender Implicit Association Test, (b) do not show that the effect of stressor relevance is more pronounced on those hemodynamic parameters typically increased by the stressor, and (c) reveal differential effects of stressor relevance for subjective and cardiovascular stress responses. Taken together, it can be concluded that the process of the cognitive appraisal of stressor relevance outlines individual variability in cardiovascular responding to acute stress.
Evaluation of a Brief Parent Intervention Teaching Coping-Promoting Behavior for the Infant Immunization Context
Authors: Bustos Theona , Jaaniste Tiina , Salmon Karen , Champion G. David
Published: June 2008

This study was designed to investigate whether a brief intervention encouraging parental coping-promoting talk within the treatment room would have beneficial effects on infant pain responses to an immunization injection. Infant-parent dyads were recruited from a 6-month immunization clinic and randomized to an intervention group ( n = 25) or standard care control group ( n = 25). Parents in the intervention group received an information sheet describing adult verbalizations associated with better pain outcomes for infants. The immunization procedure was videotaped. Parents in the intervention condition made significantly more coping-promoting statements than parents in the control condition. Infants in the control condition cried significantly longer than infants in the intervention condition. Coping-promoting and distress-promoting statements did not differ in terms of affective quality. Infants whose parents had rated them as more difficult in temperament cried longer following the injection. Teaching parents to engage in coping-promoting behaviors within the infant treatment room is an effective, low-cost intervention.
Clinical Pearls and Strategies to Optimize Patient Outcomes
Authors: Joy Scott V.
Published: June 2008

Increasing evidence suggests that a large proportion of patients with type 2 diabetes do not meet glycemic targets. Early diagnosis, realistic goal setting, improved patient adherence, and a better understanding of the pharmacotherapeutic treatment options are crucial to improving diabetes treatment outcomes in the United States. There are many reasons why patients do not achieve glycemic control. Barriers faced by clinicians, such as clinical inertia, lack of education time, and inappropriate use and titration of medications, need to be overcome to improve patient care. At the same time, patients are challenged by lifestyle management, lack of understanding of therapeutic options, and failing to see themselves as partners in their own care. Successful diabetes management programs incorporate several key features, including proactive reminders, consistent follow-up procedures, and use of clinical information systems to improve patient adherence and overall quality of care. Both clinicians and patients face barriers to advancing to injectable medications. Patients' attitudes may include fears of injections, technical challenges, and “punishment” for “failing” treatment. Clinicians have concerns about inadequate resources to address the needs of patients, patient nonadherence, and hypoglycemic events associated with certain injectable medications. Many of the strategies to overcome these barriers are reviewed.
Beyond Glycemic Control
Authors: Martin Catherine L.
Published: June 2008

The improved understanding of glucoregulatory hor- mones has driven the development of new pharmacologic agents to treat type 2 diabetes. One new class of antihy- perglycemic medication is incretin mimetics (IMs). Incretin hormones potentiate insulin secretion following meal ingestion, a process that is impaired in patients with type 2 diabetes. GLP-1, a 30–amino acid peptide incretin hormone, is produced in the L cells of the ileum and colon. Studies have shown that a 6-week continuous GLP-1 infusion in patients with type 2 diabetes improved glycemic control and β-cell function and delayed gastric emptying. Despite the rapid degradation and inactivation of GLP-1 by the enzyme dipeptidyl peptidase IV (DPP- IV), agents that mimic the actions of GLP-1 are of great clinical interest. First-in-class IM exenatide, a GLP-1 receptor agonist resistant to DPP-IV inactivation, mimics many beneficial glucoregulatory effects of GLP-1, such as suppressing glucagon secretion, regulating gastric emptying and satiety, and increasing glucose-dependent insulin secretion. Exenatide is an adjunctive therapy for patients who take metformin, a sulfonylurea, a thiazo- lidinedione, or a combination of these oral medications but have not achieved glycemic control. An 82-week, open-label extension trial has shown that exenatide is well tolerated and that the benefits, including improved glycemic control, weight loss, and mitigation of cardio- vascular risk factors, are sustained.
All in the Timing
Authors: Ballard Dawna I. , Tschan Franziska , Waller Mary J.
Published: June 2008

The role of time in measuring group and team temporality constitutes more than a methodological issue—it is a theoretical question. That is, if group interaction is theorized as processual and processes occur through time, then research on team temporality, as well as a range of other issues, must grapple with the methodological implications of our theories. This article contributes to INGRoup's aim to advance theory and methods for understanding groups by exploring methodological approaches that allow us to capture a variety of team processes over time. Three case studies address the practical issues involved with employing various types of time-sensitive data collection, time-dependent coding, and time-based analysis, including their advantages and disadvantages. Together, the authors describe diverse field and analytical methods useful for interrogating theoretical assumptions about time in groups. Doing so expands the notion of group temporality to consider the role of both epochal and fungible times at multiple stages of group research.
The Pros and Cons of Dyadic Side Conversations in Small Groups
Authors: Swaab Roderick I. , Phillips Katherine W. , Diermeier Daniel , Husted Medvec Victoria
Published: June 2008

This research explores the impact of dyadic side conversations on group norms within three- and four-person groups. The authors propose a link between dyadic communication and group norms such that the absence of dyadic communication enhances a norm of group unity, whereas its presence enhances a norm of faction-forming. In two studies, we demonstrate that the presence of dyadic communication opportunities can both help and hurt group performance and that this depends on a fit between the content of the norm and the wider social context. In negotiation tasks that benefit from group unity, the absence of dyadic communication results in a stronger focus on the group and its future as well as increased group performance. However, in problem-solving tasks that benefit from faction-forming, the mere presence of dyadic communication opportunities leads to increased openness to unique information, disagreement, and group performance.
Critical Practices in Organizations
Authors: Messner Martin , Clegg Stewart , Kornberger Martin
Published: June 2008

This article deals with the phenomenon of criticism in organizations. Existing organizational literature, where it has addressed criticism, mostly tends to see it as an extraordinary phenomenon. By contrast, in this article, the authors argue that criticism may also originate from strongly embedded and more ordinary practices. Thus, there is a theoretical need for considering those critical practices that are structurally and/or formally institutionalized within the organization. They reflect the organizational status quo and promote a reproduction of existing structures of power/knowledge. Drawing on ideas from practice theory, institutional theory, and Foucault's analytics of power/knowledge regimes, the authors introduce a typology that distinguishes forms of criticism according to the degree to which they are coupled with particular organizational practices, their rationalities, and corresponding power relations. They then focus on those forms of criticism that are strongly linked to organizational practices and illustrate the ambiguous effects of such an “organization of criticism.”
Anti-CD38 antibody–mediated clearance of human repopulating cells masks the heterogeneity of leukemia-initiating cells
Authors: Taussig David C. , Miraki-Moud Farideh , Anjos-Afonso Fernando , Pearce Daniel J. , Allen Kirsty , Ridler Christopher , Lillington Debra , Oakervee Heather , Cavenagh Jamie , Agrawal Samir G. , Lister T. Andrew , Gribben John G. , Bonnet Dominique
Published: June 2008

Immunodeficient mice are increasingly used to assay human hematopoietic repopulating cells as well as leukemia-initiating cells. One method commonly used to isolate these rare cells is to sort cells stained with fluorochrome-conjugated antibodies into fractions, then transplant the different fractions into immunodeficient mice to test their repopulating ability. The antibodies are generally treated as being neutral in terms of their effects on the experiment. Human repopulating cells are thought to express CD34 and lack CD38. Here we present evidence that anti-CD38 antibodies have a profound inhibitory effect on engraftment of cord blood and leukemia cells. We show that this effect is Fc-mediated and can be overcome by treating mice with immunosuppressive antibodies. When this inhibitory effect is prevented, we demonstrate that the CD34+CD38+ fraction of certain acute myeloid leukemia samples contains all, or at least most, leukemia-initiating cell capacity. This study highlights the potential pitfall of antibody-mediated clearance of repopulating cells and is important for any groups working with this model. More importantly, the work suggests that there is greater variation in the phenotypes of leukemia-initiating cells than previously suggested.
Regulatory polymorphism in vitamin K epoxide reductase complex subunit 1 (VKORC1) affects gene expression and warfarin dose requirement
Authors: Wang Danxin , Chen Huizi , Momary Kathryn M. , Cavallari Larisa H. , Johnson Julie A. , Sadée Wolfgang
Published: June 2008

Warfarin dose requirements have been associated with 2 main haplotypes in VKORC1, but the responsible polymorphisms remain unknown. To search for regulatory polymorphisms, we measured allelic mRNA expression of VKORC1 in human liver, heart, and B lymphocytes. The observed 2-fold allelic mRNA expression imbalance narrowed possible candidate SNPs to −1639G>A and 1173C<T. This genotype effect was observed selectively in the liver but not in heart or lymphocytes. In vitro expression of VKORC1 gene constructs, including coding and promoter regions, failed to reveal any genotype effect on transcription and mRNA processing. Chromatin immunoprecipitation with antibodies against acetyl-histone3 and K4-trimethyl-histone3 revealed preferential association of the promoter −1639 G allele with active chromatin, consistent with enhanced mRNA expression. The minor −1639 A allele generates a suppressor E-box binding site, apparently regulating gene expression by a mechanism undetectable with reporter gene assays. A clinical association study demonstrated that promoter SNP −1639G>A, and the tightly linked intron1 SNP 1173C>T, predict warfarin dose more accurately than intron 2 SNP 1542G>C in blacks. Increased warfarin dose requirement in blacks was accounted for by lower frequency of the −1639 A allele. Therefore, −1639G>A is a suitable biomarker for warfarin dosing across ethnic populations.
Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis
Authors: Folgueras Alicia R. , de Lara Fernando Martín , Pendás Alberto M. , Garabaya Cecilia , Rodríguez Francisco , Astudillo Aurora , Bernal Teresa , Cabanillas Rubén , López-Otín Carlos , Velasco Gloria
Published: June 2008

Proteolytic events at the cell surface are essential in the regulation of signal transduction pathways. During the past years, the family of type II transmembrane serine proteases (TTSPs) has acquired an increasing relevance because of their privileged localization at the cell surface, although our current understanding of the biologic function of most TTSPs is limited. Here we show that matriptase-2 (Tmprss6), a recently described member of the TTSP family, is an essential regulator of iron homeostasis. Thus, Tmprss6−/− mice display an overt phenotype of alopecia and a severe iron deficiency anemia. These hematologic alterations found in Tmprss6−/− mice are accompanied by a marked up-regulation of hepcidin, a negative regulator of iron export into plasma. Likewise, Tmprss6−/− mice have reduced ferroportin expression in the basolateral membrane of enterocytes and accumulate iron in these cells. Iron-dextran therapy rescues both alopecia and hematologic alterations of Tmprss6−/− mice, providing causal evidence that the anemic phenotype of these mutant mice results from the blockade of intestinal iron export into plasma after dietary absorption. On the basis of these findings, we conclude that matriptase-2 activity represents a novel and relevant step in hepcidin regulation and iron homeostasis.
CXCL10+ T cells and NK cells assist in the recruitment and activation of CXCR3+ and CXCL11+ leukocytes during Mycobacteria-enhanced colitis
Authors: Singh Udai P , Singh Rajesh , Singh Shailesh , Karls Russell K , Quinn Frederick D , Taub Dennis D , Lillard James W
Published: June 2008

Background

The role ofMycobacteriain the etiology of Crohn's disease (CD) has been a contentious subject for many years. Recently, our laboratory showed that spontaneous colitis in IL-10-/-mice is driven in part by antigens (Ags) conserved inMycobacteria. The present study dissects some of the common cellular and molecular mechanism that driveMycobacteria-mediated and spontaneous colitis in IL-10-/-mice.

Results

We show that serum from inflammatory bowel disease (IBD) patients contain significantly higher levels ofMycobacterium avium paratuberculosis-specific IgG1 and IgG2 antibodies (Abs), serum amyloid A (SAA) as well as CXCR3 ligands than serum from healthy donors. To study the cellular mechanisms ofMycobacteria-associated colitis, pathogen-free IL-10-/-mice were given heat-killed or liveM. avium paratuberculosis. The numbers of mucosal T cells, neutrophils, NK/NKT cells that expressed TNFα, IFN-γ, and/or CXCL10 were significantly higher in mice that received liveMycobacteriathan other groups. The numbers of mucosal CXCR3+, CXCL9+, CXCL11+and/or IFN-γ+dendritic cells (DCs) were also significantly higher inM. avium paratuberculosis-challenged mice, than compared to control mice.

Conclusion

The present study shows that CD and UC patients mount significantMycobacteria-specific IgG1 > IgG2 and CXCR3 ligand responses. Several cellular mechanisms that drive spontaneous colitis also mediateMycobacteria-enhanced colitis in IL-10-/-mice. Similar to IL-10-/-mice under conventional housing, we show thatMycobacteria-challenge IL-10-/-mice housed under otherwise pathogen-free conditions develop colitis that is driven by CXCR3- and CXCR3 ligand-expressing leukocytes, which underscores another important hallmark and molecular mechanism of colitis. Together, the data show thatMycobacteria-dependent host responses, namely CXCL10+T cells and NK cells, assist in the recruitment and activation of CXCR3+and CXCL11+leukocytes to enhance colitis of susceptible hosts.