bluuebunny/crossref_metadata_2025 huggingface dataset:
A comprehensive joint replacement program for total knee arthroplasty: a descriptive study
Authors: Cook Jon R , Warren Meghan , Ganley Kathleen J , Prefontaine Paul , Wylie Jack W
Published: November 2008

Background

Total knee arthroplasty (TKA) is a commonly performed surgical procedure in the US. It is important to have a comprehensive inpatient TKA program which maximizes outcomes while minimizing adverse events. The purpose of this study was to describe a TKA program – the Joint Replacement Program (JRP) – and report post-surgical outcomes.

Methods

74 candidates for a primary TKA were enrolled in the JRP. The JRP was designed to minimize complications and optimize patient-centered outcomes using a team approach including the patient, patient's family, and a multidisciplinary team of health professionals. The JRP consisted of a pre-operative class, standard pathways for medical care, comprehensive peri-operative pain management, aggressive physical therapy (PT), and proactive discharge planning. Measures included functional tests, knee range of motion (ROM), and medical record abstraction of patient demographics, length of stay, discharge disposition, and complications over a 6-month follow-up period.

Results

All patients achieved medical criteria for hospital discharge. The patients achieved the knee flexion ROM goal of 90° (91.7 ± 5.4°), but did not achieve the knee extension ROM goal of 0° (2.4 ± 2.6°). The length of hospital stay was two days for 53% of the patients, with 39% and 7% discharged in three and four days, respectively. All but three patients were discharged home with functional independence. 68% of these received outpatient physical therapy compared with 32% who received home physical therapy immediately after discharge. Two patients (< 3%) had medical complications during the inpatient hospital stay, and 9 patients (12%) had complications during the 6-month follow-up period.

Conclusion

The comprehensive JRP for TKA was associated with satisfactory clinical outcomes, short lengths of stay, a high percentage of patients discharged home with outpatient PT, and minimal complications. This JRP may represent an efficient, effective and safe protocol for providing care after a TKA.
Exercise training enhanced myocardial endothelial nitric oxide synthase (eNOS) function in diabetic Goto-Kakizaki (GK) rats
Authors: Grijalva James , Hicks Steven , Zhao Xiangmin , Medikayala Sushma , Kaminski Pawel M , Wolin Michael S , Edwards John G
Published: November 2008

Background

Different mechanisms of diabetic-induced NO dysfunction have been proposed and central to most of them are significant changes in eNOS function as the rate-limiting step in NO bioavailability. eNOS exists in both monomeric and dimeric conformations, with the dimeric form catalyzing the synthesis of nitric oxide, while the monomeric form catalyzes the synthesis of superoxide (O2
-). Diabetic-induced shifts to decrease the dimer:monomer ratio is thought to contribute to the degradation of nitric oxide (NO) bioavailability. Exercise has long been useful in the management of diabetes. Although exercise-induced increases expression of eNOS has been reported, it is unclear if exercise may alter the functional coupling of eNOS.

Methods

To investigate this question, Goto-Kakizaki rats (a model of type II diabetes) were randomly assigned to a 9-week running program (train) or sedentary (sed) groups.

Results

Exercise training significantly (p < .05) increased plantaris muscle cytochrome oxidase, significantly improved glycosylated hemoglobin (sed: 7.33 ± 0.56%; train: 6.1 ± 0.18%), ad improved insulin sensitivity. Exercise increased both total eNOS expression and the dimer:monomer ratio in the left ventricle LV (sed: 11.7 ± 3.2%; train: 41.4 ± 4.7%). Functional analysis of eNOS indicated that exercise induced significant increases in nitric oxide (+28%) production and concomitant decreases in eNOS-dependent superoxide (-12%) production. This effect was observed in the absence of tetrahydrobiopterin (BH4), but not in the presence of exogenous BH4. Exercise training also significantly decreased NADPH-dependent O2
- activity.

Conclusion

Exercise-induced increased eNOS dimerization resulted in an increased coupling of the enzyme to facilitate production of NO at the expense of ROS generation. This shift that could serve to decrease diabetic-related oxidative stress, which should serve to lessen diabetic-related complications.
Water aerobics in pregnancy: cardiovascular response, labor and neonatal outcomes
Authors: Baciuk Erica P , Pereira Rosa I , Cecatti Jose G , Braga Angelica F , Cavalcante Sergio R
Published: November 2008

Background

To evaluate the association between water aerobics, maternal cardiovascular capacity during pregnancy, labor and neonatal outcomes.

Methods

A randomized, controlled clinical trial was carried out in which 34 pregnant women were allocated to a water aerobics group and 37 to a control group. All women were submitted to submaximal ergometric tests on a treadmill at 19, 25 and 35 weeks of pregnancy and were followed up until delivery. Oxygen consumption (VO2 max), cardiac output (CO), physical fitness, skin temperature, data on labor and delivery, and neonate outcomes were evaluated. Frequency distributions of the baseline variables of both groups were initially performed and then analysis of the outcomes was carried out. Categorical data were compared using the chi-square test, and numerical using Student's t or Mann-Whitney tests. Wilk's Lambda or Friedman's analysis of repeat measurements were applied for comparison of physical capacity, cardiovascular outcomes and maternal temperature.

Results

VO2 max and physical fitness were higher in both groups in the second trimester, returning to basal levels in the third trimester. In both groups, CO increased as pregnancy progressed and peak exercise temperature was higher than resting temperature, increasing further after five minutes of recovery and remaining at this level until 15 minutes after exercise completion. There was no difference between the two groups regarding duration (457.9 ± SD 249.6 vs 428.9 ± SD 203.2 minutes) or type of delivery. Labor analgesia was requested by significantly fewer women in the water aerobics group (27% vs 65%; RR = 0.42 95%CI 0.23–0.77). Neonatal results were similar in both groups.

Conclusion

The regular practice of moderate water aerobics by sedentary and low risk pregnant women was not detrimental to the health of the mother or the child. There was no influence on maternal cardiovascular capacity, duration of labor or type of delivery; however, there were fewer requests for analgesia during labor in the water aerobics group.
Characterization of age-related modifications of upper limb motor control strategies in a new dynamic environment
Authors: Cesqui Benedetta , Macrì Giovanna , Dario Paolo , Micera Silvestro
Published: November 2008

Background

In the past, several research groups have shown that when a velocity dependent force field is applied during upper limb movements subjects are able to deal with this external perturbation after some training. This adaptation is achieved by creating a new internal model which is included in the normal unperturbed motor commands to achieve good performance. The efficiency of this motor control mechanism can be compromised by pathological disorders or by muscular-skeletal modifications such as the ones due to the natural aging process. In this respect, the present study aimed at identifying the age-related modifications of upper limb motor control strategies during adaptation and de-adaptation processes in velocity dependent force fields.

Methods

Eight young and eight elderly healthy subjects were included in the experiment. Subjects were instructed to perform pointing movements in the horizontal plane both in a null field and in a velocity dependent force field. The evolution of smoothness and hand path were used to characterize the performance of the subjects. Furthermore, the ability of modulating the interactive torque has been used as a paradigm to explain the observed discoordinated patterns during the adaptation process.

Results

The evolution of the kinematics during the experiments highlights important behavioural differences between the two groups during the adaptation and de-adaptation processes. In young subjects the improvement of movement smoothness was in accordance with the expected learning trend related to the consolidation of the internal model. On the contrary, elders did not show a coherent learning process. The kinetic analysis pointed out the presence of different strategies for the compensation of the external perturbation: older people required an increased involvement of the shoulder with a different modulation of joint torque components during the evolution of the experiments.

Conclusion

The results obtained with the present study seem to confirm the presence of different adaptation mechanisms in young and senior subjects. The strategy adopted by young subjects was to first minimize hand path errors with a secondary process that is consistent with the optimization of the effort. Elderly subjects instead, seemed to shift the importance of the two processes involved in the control loop slowing the mechanism optimizing kinematic performance and enabling more the dynamic adaptation mechanism.
Mechanisms Involved in an Increment of Multimodal Excitability of Medullary and Upper Cervical Dorsal Horn Neurons Following Cutaneous Capsaicin Treatment
Authors: Honda Kuniya , Kitagawa Junichi , Sessle Barry J , Kondo Masahiro , Tsuboi Yoshiyuki , Yonehara Yoshiyuki , Iwata Koichi
Published: November 2008

Background:

In order to evaluate mechanisms that may underlie the sensitization of trigeminal spinal subnucleus caudalis (Vc; the medullary dorsal horn) and upper cervical spinal cord (C1–C2) nociceptive neurons to heat, cold and mechanical stimuli following topical capsaicin treatment of the facial skin, nocifensive behaviors as well as phosphorylation of extracellular regulated-kinase (pERK) in Vc and C1–C2 neurons were studied in rats.

Results:

Compared to vehicle application, capsaicin application to the lateral facial skin produced 1 hour later a flare in the skin, and also induced significantly greater nocifensive behaviors to heat, cold or mechanical stimulus of the lateral facial skin. The intrathecal (i.t.) injection of the MEK inhibitor PD98059 markedly attenuated the nocifensive behaviors to these stimuli in capsaicin-treated rats. Moreover, the number of pERK-like immunoreactive (pERK-LI) cells in Vc and C1–C2 was significantly larger following the heat, cold and mechanical stimuli in capsaicin-treated rats compared with vehicle-treated rats. The number of pERK-LI cells gradually increased following progressive increases in the heat or mechanical stimulus intensity and following progressive decrease in the cold stimulus. The ERK phosphorylation in Vc and C1–C2 neurons was strongly inhibited after subcutaneous injection of the capsaicin antagonist capsazepine in capsaicin-treated rats.

Conclusion:

The present findings revealed that capsaicin treatment of the lateral facial skin causes an enhancement of ERK phosphorylation in Vc and C1–C2 neurons as well as induces nocifensive behavior to heat, cold and mechanical simulation of the capsaicin-treated skin. The findings suggest that TRPV1 receptor mechanisms in rat facial skin influence nociceptive responses to noxious cutaneous thermal and mechanical stimuli by inducing neuroplastic changes in Vc and C1–C2 neurons that involve in the MAP kinase cascade.
T-614, a novel immunomodulator, attenuates joint inflammation and articular damage in collagen-induced arthritis
Authors: Du Fang , Lü Liang-jing , Fu Qiong , Dai Min , Teng Jia-lin , Fan Wei , Chen Shun-le , Ye Ping , Shen Nan , Huang Xin-fang , Qian Jie , Bao Chun-de
Published: November 2008

Introduction

T-614 is a novel oral antirheumatic agent for the treatment of rheumatoid arthritis. Whether it has immunomodulatory or disease-modifying properties and its mechanism of action are largely undetermined.

Methods

Rats with collagen-induced arthritis (CIA) were treated with T-614 (5 and 20 mg/kg) daily. Animals receiving methotrexate (1 mg/kg every 3 days) and the nonsteroidal anti-inflammatory agent nimesulide (10 mg/kg per day) were used as controls. A combination therapy group was treated with both T-614(10 mg/kg per day) and methotrexate (1 mg/kg every 3 days). Hind paw swelling was evaluated and radiographic scores calculated. Serum cytokine levels were assessed by Bio-plex analysis. Quantitative PCR was used to evaluate expression of mRNA for interferon-γ, IL-4 and IL-17. Serum IL-17 and anti-type II collagen antibodies (total IgG, IgG1, IgG2a, IgG2b and IgM) were measured using ELISA.

Results

Oral T-614 inhibited paw swelling and offered significant protection against arthritis-induced cartilage and bone erosion, comparable to the effects of methotrexate. CIA rats treated with T-614 exhibited decreases in both mRNA expression of IL-17 in peripheral blood mononuclear cells and lymph node cells, and circulating IL-17 in a dose-dependent manner. T-614 also reduced serum levels of tumor necrosis factor-α, IL-1β and IL-6. A synergistic effect was observed for the combination of methotrexate and T-614. In addition, T-614 (20 mg/kg per day) depressed production of anti-type II collagen antibodies and differentially affected levels of IgG2a subclasses in vivo, whereas IgM level was decreased without any change in the IgG1 level. Together, the findings presented here indicate that the novel agent T-614 has disease-modifying effects against experimental arthritis, as opposed to nimesulide.

Conclusions

Our data suggested that T-614 is an effective disease-modifying agent that can prevent bone/cartilage destruction and inflammation in in CIA rats. Combination with methotrexate markedly enhances the therapeutic effect of T-614.
ErbB3 is required for ductal morphogenesis in the mouse mammary gland
Authors: Jackson-Fisher Amy J , Bellinger Gary , Breindel Jerrica L , Tavassoli Fatteneh A , Booth Carmen J , Duong James K , Stern David F
Published: November 2008

Introduction

The receptor ErbB3/HER3 is often over-expressed in human breast cancers, frequently in conjunction with over-expression of the proto-oncogene ERBB2/HER2/NEU. Although the prognostic/predictive value of ErbB3 expression in breast cancer is unclear, ErbB3 is known to contribute to therapeutic resistance. Understanding ErbB3 functions in the normal mammary gland will help to explain its role in cancer etiology and as a modulator of signaling responses to the mammary oncogene ERBB2.

Methods

To investigate the roles of ErbB3 in mouse mammary gland development, we transplanted mammary buds from ErbB3-/- embryos into the cleared mammary fat pads of wild-type immunocompromised mice. Effects on ductal outgrowth were analyzed at 4 weeks, 7 weeks and 20 weeks after transplantation for total ductal outgrowth, branch density, and number and area of terminal end buds. Sections of glands containing terminal end buds were analyzed for number and epithelial area of terminal end buds. Terminal end buds were also analyzed for presence of mitotic figures, apoptotic figures, BrdU incorporation, and expression of E-cadherin, P-cadherin, α-smooth muscle actin, and cleaved caspase-3.

Results

The mammary ductal trees developed from ErbB3-/- buds only partly filled the mammary fat pad. In contrast to similar experiments with ErbB2-/- mammary buds, this phenotype was maintained through adulthood, pregnancy, and parturition. In addition, and in contrast to similar work with ErbB4-/- mammary buds, lobuloalveolar development of ErbB3-/- transplanted glands was normal. The ErbB3-/- mammary outgrowth defect was associated with a decrease in the size of the terminal end buds, and with increases in branch density, in the number of terminal end buds, and in the number of luminal spaces. Proliferation rates were not affected by the lack of ErbB3, but there was an increase in apoptosis in ErbB3-/- terminal end buds.

Conclusions

Endogenous ErbB3 regulates morphogenesis of mammary epithelium.
Continued Regulatory Actions Affecting the Use of Erythropoiesis-Stimulating Agents
Authors: Hagerty Karen
Published: November 2008

The FDA sent a “Complete Response and Safety Labeling Change Order” to the sponsors of ESAs on July 30, ordering changes to ESA labels in three important ways. For the first time, the FDA used its statutory authority to order a sponsor to make revisions to a product label.
Cigarette Smoking during Pregnancy Is Associated with Alterations in Maternal and Fetal Thyroid Function
Authors: Shields Beverley , Hill Anita , Bilous Mary , Knight Beatrice , Hattersley Andrew T. , Bilous Rudy W. , Vaidya Bijay
Published: November 2008

Context: Studies in the general population have shown lower serum TSH levels in smokers as compared with nonsmokers.

Aim: Our aim was to examine whether smoking is associated with changes in thyroid function of pregnant women and their fetus.

Subjects and Methods: We examined the relationship between smoking and thyroid function (serum TSH, free T4, and free T3) in two independent cohorts of pregnant women without a history of thyroid disorder or an overt biochemical thyroid dysfunction: 1) first-trimester cohort (median gestation 9 wk) (n = 1428) and 2) third-trimester cohort (gestation 28 wk) (n = 927). We also analyzed the relationship between maternal smoking and thyroid hormone levels in cord serum of 618 full-term babies born to the women in the third-trimester cohort.

Results: In smokers compared with nonsmokers, median serum TSH was lower (first-trimester cohort: 1.02 vs. 1.17 mIU/liter, P = 0.001; third-trimester cohort: 1.72 vs. 1.90 mIU/liter, P = 0.037), and median serum FT3 was higher (first-trimester cohort: 5.1 vs. 4.9 pmol/liter, P < 0.0001; third-trimester cohort: 4.4 vs. 4.1 pmol/liter, P < 0.0001). In both cohorts, serum FT4 in smokers and nonsmokers were similar. The prevalence of anti-thyroperoxidase antibodies was also similar in smokers and nonsmokers in both cohorts. Cord serum TSH of babies born to smokers was lower than of those born to nonsmokers (6.7 vs. 8.1 mIU/liter, P = 0.009).

Conclusions: Cigarette smoking is associated with changes in maternal thyroid function throughout the pregnancy and in fetal thyroid function as measured in cord blood samples.
Promising, Intimate Relationships, and Conventionalism
Authors: Shiffrin Seana Valentine
Published: November 2008

The power to promise is morally fundamental and does not, at its foundation, derive from moral principles that govern our use of conventions. Of course, many features of promising have conventional components—including which words, gestures, or conditions of silence create commitments. What is really at issue between conventionalists and nonconventionalists is whether the basic moral relation of promissory commitment derives from the moral principles that govern our use of social conventions.

Other nonconventionalist accounts make problematic concessions to the conventionalist's core instincts, including embracing: the view that binding promises must involve the promisee's belief that performance will occur; the view that through the promise, the promisee and promisor create a shared end; and the tendency to take promises between strangers, rather than intimates, as the prototypes to which a satisfactory account must answer.

I argue against these positions and then pursue an account that finds its motivation in their rejection. My main claim is: the power to make promises, and other related forms of commitment, is an integral part of the ability to engage in special relationships in a morally good way. The argument proceeds by examining what would be missing, morally, from intimate relationships if we lacked this power.
The consequences of tetraploidy and aneuploidy
Authors: Storchova Zuzana , Kuffer Christian
Published: November 2008

Polyploidy, an increased number of chromosome sets, is a surprisingly common phenomenon in nature, particularly in plants and fungi. In humans, polyploidy often occurs in specific tissues as part of terminal differentiation. Changes in ploidy can also result from pathophysiological events that are caused by viral-induced cell fusion or erroneous cell division. Tetraploidization can initiate chromosomal instability (CIN), probably owing to supernumerary centrosomes and the doubled chromosome mass. CIN, in turn, might persist or soon give way to a stably propagating but aneuploid karyotype. Both CIN and stable aneuploidy are commonly observed in cancers. Recently, it has been proposed that an increased number of chromosome sets can promote cell transformation and give rise to an aneuploid tumor. Here, we review how tetraploidy can occur and describe the cellular responses to increased ploidy. Furthermore, we discuss how the specific physiological changes that are triggered by polyploidization might be used as novel targets for cancer therapy.
Translational and rotational aerodynamic drag of composite construction bicycle wheels
Authors: Jermy M , Moore J , Bloomfield M
Published: November 2008

Drag and side force measurements were made in a wind tunnel on disc wheels, deep-rim wire-spoked wheels, and ‘aero’ spoke wheels, which have three to five aerodynamically shaped compression spokes. The wheels were run at 30–50 kph and yaw angles from zero up to 50° yaw, covering the range of crosswinds usually experienced in outdoor races. Unlike previous studies, translational and rotational aerodynamic power losses are measured and reported separately.

The disc wheels have the lowest power losses, but the ‘aero’ spoke wheels require little more power than the discs; the wire-spoke wheels require the most power. The best wire-spoke wheels experience less side force in crosswind than the aero wheels, although the best aero wheel tested approaches the side force performance of one of the wire-spoke wheels. Side force correlates with side projected area.

Rotational drag affects the total drag significantly, and the choice of wheel should not be based on translational drag alone.
Do men and women row differently? a spinal kinematic and force perspective
Authors: McGregor A H , Patankar Z S , Bull A M J
Published: November 2008

Performance differences have been noted between male and female rowers; the aim of this study was to determine if these are due to differences in rowing technique. An electromagnetic motion measurement device in conjunction with a load cell was used to compare the ergometer rowing kinematics of female and male elite national rowers.

Male rowers generated significantly greater peak force during the stroke, ( p < 0.0001) and greater power. Although there was no difference in stroke length, females demonstrated a more optimal lumbopelvic rhythm due to a greater anterior pelvic rotation during the stroke ( p < 0.05). This is likely to account for the lack of difference in stroke length. In conclusion, gender differences do exist in kinematic parameters of rowing technique. With a greater mass and height, the male athletes are more powerful than the females; however, females appear to optimize their kinematics in an attempt to enhance performance.
Screening for abdominal aortic aneurysms: some legal implications
Authors: Elliott Tracey
Published: November 2008

This article explores some of the main legal implications of abdominal aortic aneurysm (AAA) scanning and treatment, particularly in relation to the interpretation of AAA scans, the provision of patients with adequate information about their options and the risks involved, and issues in relation to monitoring, re-scanning and re-calling the patient for further assessment and treatment. It is suggested that the introduction of national AAA scanning programme is likely to lead to an increase in litigation claims in this field, and that, given the complex nature of the risk–benefit assessment in relation to AAA treatment, particular care needs to be taken to ensure that patients are properly informed about their condition and its treatment, if Chester v Afshar-type claims are to be avoided.
Masters of War: Rivals' Product Innovation and New Advertising in Mature Product Markets
Authors: Fosfuri Andrea , Giarratana Marco S.
Published: November 2008

We investigate the impact of rivals' product innovation and new advertising on a firm's financial market value in mature product markets. Our test bed is the carbonated soft drink market between 1999 and 2003, a period characterized by a near duopoly between Coca-Cola and Pespi. Empirically, we focus on new product announcements as a proxy of product innovation and on filed trademarks as a measure of new advertising. We find that rival product announcements decrease a firm's financial market value, and that rival filed trademarks increase it. Finally, we find that the effect of new advertising is channeled through market size dynamics, while that of product innovation operates through market share dynamics. Results are robust across different estimation techniques (event study, Tobin's q) and model specifications.
Scanning the Commons? Evidence on the Benefits to Startups Participating in Open Standards Development
Authors: Waguespack David M. , Fleming Lee
Published: November 2008

This paper contributes large-sample evidence to an emerging discussion on open innovation and firm strategy. We ask why a startup should participate in an open standards community. We propose four ways that participation might increase a startup's chances of a liquidity event: gaining endorsement of the startup's technology standard, openly developing the startup's technology within the community (but not necessarily gaining endorsement), simply attending physical meetings of the community, and having startup members elected to leadership positions. Examination of venture-funded startups in the networking/data communications industry sectors reveals that those startups that participate in an open standards community (the Internet Engineering Task Force (IETF)) have a greater likelihood of an initial public offering or acquisition. The strongest effects are due to attendance, and conditional on high levels of attendance, holding leadership positions within the IETF. Surprisingly, standards endorsement is insignificant when controlling for simple physical attendance. These results are robust to instrumental variable methods and alternative coding of variables. In two-stage models we also find that prominent venture capitalists might help their portfolio companies by steering them to effective technology strategies, in this case active participation in the IETF, and not simply by lending status.
Optimization Models of Discrete-Event System Dynamics
Authors: Chan Wai Kin (Victor) , Schruben Lee
Published: November 2008

A methodology is given for modeling the dynamics of discrete-event stochastic systems as optimization problems. The intent is to provide a means to utilize the rich mathematical theory and algorithms of optimization in the study of this important class of systems. A procedure for mapping a simulation event relationship graph into a mixed-integer program is presented, along with examples of queueing networks and manufacturing systems that illustrate the approach. Several potential applications are examined, including automatic constraint generation for optimal resource scheduling, representations of max-plus algebra models for queueing system dynamics, response gradient estimation, and an unconventional technique for simulating queueing systems using virtual resources that are identified from the optimization models for these systems.
Technical Note—A Risk-Sensitive Model for Managing Perishable Products
Authors: Feng Youyi , Xiao Baichun
Published: November 2008

This article presents a risk-sensitive model for managing perishable products assuming the supplier is averse to the variation of revenues. While traditional risk-neutral revenue management models offer optimal strategies in the long run, they are exposed to the variation of revenue flows. If a short-term revenue target is a primary concern for the supplier, the risk-neutral assumption fails to provide the best policy needed. The proposed model uses an exponential function with a risk-sensitive parameter instead of the conventional risk-neutral objective. The risk parameter measures how the supplier is sensitive to the deviation of revenues. We show that the new objective function captures the supplier's risk behavior. We develop a recursive procedure for the optimal solution in closed form. The optimal policy has attractive properties such as nested active price set, monotonicity with respect to the remaining time and inventory, and threshold-type control. When the supplier is more sensitive to the uncertain revenue flows, the risk-sensitive model leads to more conservative pricing policies. Finally, we show that the risk-neutral model is a special case of the proposed framework.
Joint Inventory and Pricing Decisions for an Assortment
Authors: Aydin Goker , Porteus Evan L.
Published: November 2008

We seek optimal inventory levels and prices of multiple products in a given assortment in a newsvendor model (single period, stochastic demand) under price-based substitution, but not stockout-based substitution. We address a demand model involving multiplicative uncertainty, motivated by market share models often used in marketing. The pricing problem that arises is known not to be well behaved in the sense that, in its deterministic version, the objective function is not jointly quasi-concave in prices. However, we find that the objective function is still reasonably well behaved in the sense that there is a unique solution to the first-order conditions, and this solution is optimal for our problem.
Analysis of the (Q, r) Inventory Model for Perishables with Positive Lead Times and Lost Sales
Authors: Berk Emre , Gürler Ülkü
Published: November 2008

We consider a perishable inventory system with Poisson demands, fixed shelf lives, constant lead times, and lost sales in the presence of nonnegligible fixed ordering costs. The inventory control policy employed is the continuous-review (Q,r) policy, where r<Q. The system is modeled using an embedded Markov process approach by introducing the concept of the effective shelf life of a batch in use. Using the stationary distribution of the effective shelf life, we obtain the expressions for the operating characteristics and construct the expected cost rate function for the inventory system. Our numerical study indicates that the determination of the policy parameters exactly as modeled herein results in significant improvements in cost rates with respect to a previously proposed heuristic. We also compare the (Q,r) policy with respect to a time-based benchmark policy and find that the (Q,r) policy might be impractical for rare events, but overall appears to be a good heuristic policy.
Successful Treatment of Fosinopril-Induced Severe Cholestatic Jaundice with Plasma Exchange
Authors: Chou Jen-Wei , Yu Cheng-Ju , Chuang Po-Heng , Lai Hsueh-Chou , Hsu Chang-Hu , Cheng Ken-Sheng , Peng Cheng-Yuan , Chiang I-Ping
Published: November 2008

Objective:

To describe a case of fosinopril-induced severe cholestatic jaundice successfully treated with plasma exchange.

Case Summary:

A 78-year-old Taiwanese male presented with yellowish skin and generalized itching one month after starting fosinopril 10 mg once a day. Other drugs taken by the patient were excluded as the probable cause of jaundice. Diagnostic modalities, including abdominal ultrasound, computed tomography, and endoscopic retrograde cholangiopancreatography, revealed no evidence of biliary tract obstruction or intraabdominal tumor. According to the Council for International Organizations of Medical Science (CIOMS) scale, fosinopril was a highly probable cause of the patient's jaundice. Liver biopsy showed cholestasis without bile duct damage. Based on results of the CIOMS scale assessment and pathological characteristics of the liver, the diagnosis was highly probable that fosinopril had induced cholestatic jaundice in our patient. During hospitalization, the patient developed severe jaundice and liver failure, despite conservative treatment and withdrawal of fosinopril. He underwent a 5-day course of plasma exchange therapy, and the serum bilirubin level declined rapidly after treatment. His liver function returned to normal 2 months after treatment.

Discussion:

Angiotensin-converting enzyme (ACE) inhibitor–induced hepatotoxicity is rare and only a few cases, with most involving captopril, have been reported in the English-language literature. Hepatotoxicity caused by fosinopril is extremely rare. Most ACE inhibitor–induced hepatotoxicity is mild and transient, but it can be fatal. Although orthotopic liver transplantation (OLT) is the standard method for treating drug-induced liver failure, plasma exchange therapy is an alternative therapeutic method or a bridge to OLT for treating liver failure.

Conclusions:

Plasma exchange therapy may play a valuable role in the treatment of fosinopril-induced cholestatic jaundice and liver failure. This intervention can be considered for temporary liver support until recovery or OLT.
A Primer on Critical Care Pharmacy Services
Authors: Erstad Brian L
Published: November 2008

The intensive care unit (ICU) continues to be a major focus of decentralized pharmacy activities in health systems that care for critically ill patients. This is not surprising, given the need for rapid decision-making involving unstable patients, the large number of powerful medications typically used per patient, the high cost of many drugs used in the ICU and, most importantly, the evidence demonstrating the benefits of having a pharmacist as part of an interdisciplinary team. The purpose of this paper is to highlight important issues to consider when introducing or developing critical care pharmacy services beginning with the establishment of basic services and continuing through practitioner development, guideline/protocol development and implementation, patient safety, residency training, and research.
Almost g.o. spaces in dimensions 6 and 7
Authors: Dušek Zdeněk
Published: November 2008

Some pseudo-Riemannian modifications of 6-dimensional and 7-dimensional Riemannian g.o. spaces are presented as pseudo-Riemannian homogeneous spaces with noncompact isotropy groups. These examples have the property that all geodesics are homogeneous up to a set of measure zero. Based on these examples, conjectures on geodesic graphs are formulated.
Constant-Rate-of-Strain and Controlled-Gradient Consolidation Testing
Authors: Gorman CT , Hopkins TC , Deen RC , Drnevich VP
Published: November 2008

Controlled-gradient (CG), constant-rate-of-strain (CRS), and conventional incremental-loading (STD) consolidation testing are compared and evaluated. Undisturbed samples of three soils common to Kentucky were used in the testing program. Results of 15 CG, 14 CRS, and 32 STD consolidation tests are evaluated. The feasibility of these new test methods for routine testing is briefly discussed and recommendations are made for refinements in testing procedures.
A New Apparatus for Measuring the Principal Strains in Anisotropic Clays
Authors: Yuen CMK , Lo KY , Palmer JHL , Leonards GA
Published: November 2008

An apparatus and an experimental arrangement were developed to provide an accurate measurement of the lateral deformation of soft sensitive clays. The apparatus contained light gage points and displacement transducers floated in a cell fluid in such a way that internal strains could be measured directly on the soil specimen with the least amount of disturbance. The performance data obtained from the testing of a soft sensitive clay indicated that the apparatus developed possessed adequate precision and stability for the study of the deformation behavior of clays.
Minimum and Maximum Densities of Granular Materials
Authors: Mehdiratta GR , Triandafilidis GE
Published: November 2008

Laboratory tests were conducted to determine minimum and maximum densities of arroyo sand, concrete sand, Ottawa sand, and glass beads. Minimum densities were determined by six different methods using two different molds. Maximum density tests were performed using an electromagnetic vibrator producing vertical simple harmonic motion. The vibration parameters investigated were frequency, acceleration, displacement, and the duration of vibrations.

The minimum densities obtained by using the ASTM Test for Relative Density of Cohesionless Soils (D 2049-69) were considerably higher than those obtained by using several other simple procedures. Acceleration appeared to be the most important vibration parameter, and accelerations greater than the optimum acceleration (the acceleration at which the maximum density of a soil was obtained) caused a decrease in the maximum density. We recommend that these tests be performed at different amplitudes of acceleration and that the acceleration be continuously monitored during the test. A simple harmonic motion of the soil container gave results which were highly reproducible. We recommend that the soil container be directly attached to the moving core of the electromagnetic vibrator and that the vibrating table be eliminated.
EngrailedHomeobox Genes Determine the Organization of Purkinje Cell Sagittal Stripe Gene Expression in the Adult Cerebellum
Authors: Sillitoe Roy V. , Stephen Daniel , Lao Zhimin , Joyner Alexandra L.
Published: November 2008

Underlying the seemingly uniform cellular composition of the adult mammalian cerebellum (Cb) are striking parasagittal stripes of gene expression along the medial-lateral (ML) axis that are organized with respect to the lobules that divide the Cb along the anterior–posterior (AP) axis. Although there is a clear correlation between the organization of gene expression stripes and Cb activity patterns, little is known about the genetic pathways that determine the intrinsic stripe molecular code. Here we establish that ML molecular code patterning is highly dependent on two homeobox transcription factors, Engrailed1 (En1) and En2, both of which are also required for patterning the lobules. Gene expression analysis of an allelic series ofEn1/2mutant mice that have an intact Purkinje cell layer revealed severe patterning defects using three known components of the ML molecular code and a new marker of Hsp25 negative stripes (Neurofilament heavy chain, Nfh). Importantly, the complementary expression of ZebrinII/PhospholipaseCβ4 and Hsp25/Nfh changes in unison in each mutant. Furthermore, eachEngene has unique as well as overlapping functions in patterning the ML molecular code and each En protein has dominant functions in different AP domains (subsets of lobules). Remarkably, inEn1/2mutants with almost normal foliation, ML molecular code patterning is severely disrupted. Thus, independent mechanisms that useEn1/2must pattern foliation and spatial gene expression separately. Our studies reveal thatEn1/2are fundamental components of the genetic pathways that pattern the two intersecting coordinate systems of the Cb, morphological divisions and the molecular code.
Zebrafish Dorsal Root Ganglia Neural Precursor Cells Adopt a Glial Fate in the Absence ofNeurogenin1
Authors: McGraw Hillary F. , Nechiporuk Alexei , Raible David W.
Published: November 2008

The proneural transcription factorneurogenin 1(neurog1) has been shown to be a key regulator of dorsal root ganglion (DRG) neuron development. Here we use a novel transgenic zebrafish line to demonstrate that the neural crest population that gives rise to DRG neurons becomes fate restricted to a neuronal/glial precursor before the onset ofneurog1function. We generated a stable transgenic zebrafish line that carries a modified bacterial artificial chromosome that expresses green fluorescent protein (GFP) under the control of theneurog1promoter [Tg(neurog1:EGFP)]. In contrast to previously describedneurog1transgenic lines,Tg(neurog1:EGFP)expresses GFP in DRG neuronal precursors cells as they migrate ventrally and after their initial differentiation as neurons. Using this line, we are able to track the fate of DRG neuronal precursor cells during their specification. When Neurog1 function is blocked, either byneurog1morpholino antisense oligonucleotide injection or inneurog1mutants, GFP expression initiates in neural crest cells, although they fail to form DRG neurons. Rather, these cells take on a glial-like morphology, retain proliferative capacity, and express glial markers and become associated with the ventral motor root. These results suggest that, within the zebrafish neural crest, there is a fate-restricted lineage that is limited to form either sensory neurons or glia in the developing DRG. Neurog1 acts as the key factor in this lineage to direct the formation of sensory neurons.
Imaging of Peripheral Benzodiazepine Receptor Expression as Biomarkers of Detrimental versus Beneficial Glial Responses in Mouse Models of Alzheimer's and Other CNS Pathologies
Authors: Ji Bin , Maeda Jun , Sawada Makoto , Ono Maiko , Okauchi Takashi , Inaji Motoki , Zhang Ming-Rong , Suzuki Kazutoshi , Ando Kiyoshi , Staufenbiel Matthias , Trojanowski John Q. , Lee Virginia M. Y. , Higuchi Makoto , Suhara Tetsuya
Published: November 2008

We demonstrate the significance of peripheral benzodiazepine receptor (PBR) imaging in living mouse models of Alzheimer's disease (AD) as biomarkers and functional signatures of glial activation. By radiochemically and immunohistochemically analyzing murine models of the two pathological hallmarks of AD, we found that AD-like Aβ deposition is concurrent with astrocyte-dominant PBR expression, in striking contrast with nonastroglial PBR upregulation in accumulations of AD-like phosphorylated tau. Because tau-induced massive neuronal loss was distinct from the marginal neurodegeneration associated with Aβ plaques in these models, cellular localization of PBR reflected deleterious and beneficial glial reactions to tau versus Aβ pathologies, respectively. This notion was subsequently examined in models of various non-AD neuropathologies, revealing the following reactive glial dynamics underlying differential PBR upregulation: (1) PBR(−) astrogliosis uncoupled with microgliosis or coupled with PBR(+) microgliosis associated with irreversible neuronal insults; and (2) PBR(+) astrogliosis coupled with PBR(− or ±) microgliosis associated with minimal or reversible neuronal toxicity. Intracranial transplantation of microglia also indicated that nontoxic microglia drives astroglial PBR expression. Moreover, levels of glial cell line-derived neurotrophic factor (GDNF) in astrocytes were correlated with astroglial PBR, except for increased GDNF in PBR(-) astrocytes in the model of AD-like tau pathology, thereby suggesting that PBR upregulation in astrocytes is an indicator of neurotrophic support. Together, PBR expressions in astrocytes and microglia reflect beneficial and deleterious glial reactions, respectively, in diverse neurodegenerative disorders including AD, pointing to new applications of PBR imaging for monitoring the impact of gliosis on the pathogenesis and treatment of AD.
Blocking Aβ42Accumulation Delays the Onset and Progression of Tau Pathology via the C Terminus of Heat Shock Protein70-Interacting Protein: A Mechanistic Link between Aβ and Tau Pathology
Authors: Oddo Salvatore , Caccamo Antonella , Tseng Bert , Cheng David , Vasilevko Vitaly , Cribbs David H. , LaFerla Frank M.
Published: November 2008

The molecular alterations that induce tau pathology in Alzheimer disease (AD) are not known, particularly whether this is an amyloid-β (Aβ)-dependent or -independent event. We addressed this issue in the 3xTg-AD mice using both genetic and immunological approaches and show that a selective decrease in Aβ42markedly delays the progression of tau pathology. The mechanism underlying this effect involves alterations in the levels of C terminus of heat shock protein70-interacting protein (CHIP) as we show that Aβ accumulation decreases CHIP expression and increases tau levels. We show that the Aβ-induced effects on tau were rescued by restoring CHIP levels. Our findings have profound clinical implications as they indicate that preventing Aβ accumulation will significantly alter AD progression. These data highlight the critical role CHIP plays as a link between Aβ and tau and identify CHIP as a new potential target not only for AD but for other neurodegenerative disorders characterized by tau accumulation.
Separate Areas for Mirror Responses and Agency within the Parietal Operculum
Authors: Agnew Zarinah , Wise Richard J. S.
Published: November 2008

There is common neural activity in parietal and premotor cortex when executing and observing goal-directed movements: the “mirror” response. In addition, active and passive limb movements cause overlapping activity in premotor and somatosensory cortex. This association of motor and sensory activity cannot ascribe agency, the ability to discriminate between self- and non-self-generated events. This requires that some signals accompanying self-initiated limb movement dissociate from those evoked by observing the action of another or by movement imposed on oneself by external force. We demonstrated associated activity within the medial parietal operculum in response to feedforward visual or somatosensory information accompanying observed and imposed finger movements. In contrast, the response to motor and somatosensory information during self-initiated finger and observed movements resulted in activity localized to the lateral parietal operculum. This ascribes separate functions to medial and lateral second-order somatosensory cortex, anatomically dissociating the agent and the mirror response, demonstrating how executed and observed events are distinguished despite common activity in widespread sensorimotor cortices.
Thermotaxis is a Robust Mechanism for Thermoregulation inCaenorhabditis elegansNematodes
Authors: Ramot Daniel , MacInnis Bronwyn L. , Lee Hau-Chen , Goodman Miriam B.
Published: November 2008

Many biochemical networks are robust to variations in network or stimulus parameters. Although robustness is considered an important design principle of such networks, it is not known whether this principle also applies to higher-level biological processes such as animal behavior. In thermal gradients,Caenorhabditis elegansuses thermotaxis to bias its movement along the direction of the gradient. Here we develop a detailed, quantitative map ofC. elegansthermotaxis and use these data to derive a computational model of thermotaxis in the soil, a natural environment ofC. elegans. This computational analysis indicates that thermotaxis enables animals to avoid temperatures at which they cannot reproduce, to limit excursions from their adapted temperature, and to remain relatively close to the surface of the soil, where oxygen is abundant. Furthermore, our analysis reveals that this mechanism is robust to large variations in the parameters governing both worm locomotion and temperature fluctuations in the soil. We suggest that, similar to biochemical networks, animals evolve behavioral strategies that are robust, rather than strategies that rely on fine tuning of specific behavioral parameters.