bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Comparison of Anteromedial versus Anterolateral Tibial Tunnel Direction for Transtibial Posterior Cruciate Ligament Reconstruction
Authors: Kim Sung-Jae , Chang Ji-Hoon , Kang Yung-Hoon , Song Dae-Heup , Park Kwang-Yeol
Published: March 2009

Background

It has been suggested that transtibial posterior cruciate ligament reconstruction may be compromised by graft abrasion at the “killer turn,” where the graft emerges from the tibia. In 1998, one of the authors suggested that beginning the tibial tunnel anterolaterally rather than anteromedially would reduce the killer turn and possibly improve the results of posterior cruciate ligament reconstruction.

Purpose

This article is intended to present the clinical results of single-bundle transtibial posterior cruciate ligament reconstruction, comparing cases in which the tibial tunnel was begun anteromedially with cases in which the tunnel was begun anterolaterally.

Study Design

Cohort study; Level of evidence, 3.

Methods

The authors retrospectively studied 23 patients (group I) using the anteromedial tibial tunnel technique from April 1998 to August 2003 and 37 patients (group II) using the anterolateral tibial tunnel technique from February 1998 to August 2003. The average follow-up period was 58.6 months in group I and 56.9 months in group II. The minimum follow-up period was 24 months in each group. All revision cases and patients with general laxity were excluded.

Results

The mean side-to-side difference of posterior tibial translation by Telos stress radiography was 3.98 ± 1.27 mm (range, 1.80-7.80 mm) in group I and 2.87 ± 1.25 mm (range, 1.43-6.82 mm) in group II, which was a statistically significant difference ( P < .01). The final mean Lysholm knee score was 88.6 ± 7.10 points (range, 77-98 points) in group I and 88.4 ± 6.44 points (range, 78-98 points) in group II, which was not a statistically significant difference ( P = .4358). According to the final International Knee Documentation Committee (IKDC) evaluation in group I, 30.4% (7 of 23) were normal (A), 60.9% (14 of 23) were nearly normal (B), and 8.7% (2 of 23) were abnormal (C). In group II, 24.3% (9 of 37) were normal (A), 73.0% (27 of 37) were nearly normal (B), and 2.7% (1 of 37) were abnormal (C) ( P = .467). With respect to the mean side-to-side difference of range of motion, there was no statistically significant difference ( P = .1697). The mean was 4.7° ± 2.38° (range, 2°-10°) in group I and 4.0° ± 1.73° (range, 0°-8°) in group II.

Conclusion

The anterolateral tibial tunnel technique is preferred to the anteromedial technique in terms of the objective results; however, clinical results as judged by Lysholm and IKDC scores are not significantly correlated to these results.
Social Network Services as Data Sources and Platforms for e-Researching Social Networks
Authors: Ackland Robert
Published: March 2009

Social network services such as Facebook provide new data for social science research into, for example, the role of individual characteristics in friendship formation and the diffusion of tastes in social networks. This article assesses the potential of social network services for social science research in two ways. First, it is argued that social scientists conduct hyperlink analysis differently to applied physicists and researchers from the library and information sciences, and face constraints (relating to theory, methods and availability of appropriate tools) that are not encountered in the other disciplinary approaches. However, the constraints regarding theory and methods are less likely to be faced by researchers of online social networks, and for this reason, the rise of Facebook and other similar services is a potential boon for empirical social scientists interested in networks. The second part of the article focuses specifically on the availability of research tools, and it is argued that social network services may eventually serve as e-Research platforms for delivering social network analysis tools.
Fibrinogen is required for maintenance of platelet intracellular and cell-surface P-selectin expression
Authors: Yang Hong , Lang Sean , Zhai Zhimin , Li Ling , Kahr Walter H. A. , Chen Pingguo , Brkić Jelena , Spring Christopher M. , Flick Matthew J. , Degen Jay L. , Freedman John , Ni Heyu
Published: March 2009

Platelet P-selectin plays important roles in inflammation and contributes to thrombosis and hemostasis. Although it has been reported that von Willebrand factor (VWF) affects P-selectin expression on endothelial cells, little information is available regarding regulation of platelet P-selectin expression. Here, we first observed that P-selectin expression was significantly decreased on platelets of fibrinogen and VWF double-deficient mice. Subsequently, we identified this was due to fibrinogen deficiency. Impaired P-selectin expression on fibrinogen-deficient platelets was further confirmed in human hypofibrinogenemic patients. We demonstrated that this impairment is unlikely due to excessive P-selectin shedding, deficient fibrinogen-mediated cell surface P-selectin binding, or impaired platelet granule release, but rather is due to decreased platelet P-selectin content. Fibrinogen transfusion completely recovered this impairment in fibrinogen-deficient (Fg−/−) mice, and engagement of the C-terminus of the fibrinogen γ chain with β3 integrin was required for this process. Furthermore, Fg−/− platelets significantly increased P-selectin expression following transfusion into β3 integrin–deficient mice and when cultured with fibrinogen. These data suggest fibrinogen may play important roles in inflammation, thrombosis, and hemostasis via enhancement of platelet P-selectin expression. Since human fibrinogen levels vary significantly in normal and diseased populations, P-selectin as an activation marker on platelets should be used with caution.
Regulatory T-cell status in red cell alloimmunized responder and nonresponder mice
Authors: Bao Weili , Yu Jin , Heck Susanne , Yazdanbakhsh Karina
Published: March 2009

Red blood cell alloimmunization remains a major complication for transfusion-dependent patients, but immune factors governing risk for alloimmunization are unknown. We hypothesized that CD4+ regulatory T cells (Tregs), which we have shown control the rate and the frequency of red blood cell alloimmunization in mouse models, may dictate responder/nonresponder status. Using a transfusion regimen in which more than 50% of mice develop alloantibodies to human glycophorin A antigen, we found reduced in vitro and in vivo Treg-suppressive activity in responders compared with nonresponders that was the result of impaired Treg suppressor function. Moreover, responders were prone to developing additional alloantibodies to strong immunogens, whereas nonresponders were resistant to alloimmunization. Altogether, our data raise the possibility that Treg activity may be used as a marker for identifying responder/nonresponder status in transfusion recipients.
A mouse model for chronic lymphocytic leukemia based on expression of the SV40 large T antigen
Authors: ter Brugge Petra J. , Ta Van B. T. , de Bruijn Marjolein J. W. , Keijzers Guido , Maas Alex , van Gent Dik C. , Hendriks Rudi W.
Published: March 2009

The simian virus 40 (SV40) T antigen is a potent oncogene able to transform many cell types and has been implicated in leukemia and lymphoma. In this report, we have achieved sporadic SV40 T-antigen expression in mature B cells in mice, by insertion of a SV40 T antigen gene in opposite transcriptional orientation in the immunoglobulin (Ig) heavy (H) chain locus between the D and JH segments. SV40 T-antigen expression appeared to result from retention of the targeted germline allele and concomitant antisense transcription of SV40 large T in mature B cells, leading to chronic lymphocytic leukemia (CLL). Although B-cell development was unperturbed in young mice, aging mice showed accumulation of a monoclonal B-cell population in which the targeted IgH allele was in germline configuration and the wild-type IgH allele had a productive V(D)J recombination. These leukemic B cells were IgDlowCD5+ and manifested nonrandom usage of V, D, and J segments. VH regions were either unmutated, with preferential usage of the VH11 family, or manifested extensive somatic hypermutation. Our findings provide an animal model for B-CLL and show that pathways activated by SV40 T antigen play important roles in the pathogenesis of B-CLL.
Hypersensitivity pneumonitis associated with the use of temozolomide
Authors: Koschel D. , Handzhiev S. , Leucht V. , Holotiuk O. , Fisseler-Eckhoff A. , Höffken G.
Published: March 2009

The aim of the present study was to investigate a case of hypersensitivity pneumonitis associated with the use of temozolomide in the treatment of gliosarcoma.

A 54-yr-old female developed dyspnoea, cough and hypoxia after surgical resection for gliosarcoma and adjuvant radio- and chemotherapy with temozolomide. A high-resolution computed tomography scan of the thorax showed a bilateral ground-glass pattern. Bronchoscopy with bronchoalveolar lavage and lung biopsies was performed.

Bronchoalveolar lavage demonstrated significant lymphocytic alveolitis and transbronchial lung biopsies revealed lymphocytic infiltration with foamy macrophages, consistent with hypersensitivity pneumonitis. There was no evidence of other causes, including infections. After withdrawing temozolomide and initiating prednisolone therapy, the patient had no further pulmonary symptoms.

To the present authors’ knowledge, this is the first definitively described case of temozolomide-associated hypersensitivity pneumonitis.
First- and second-line therapy for advanced nonsmall cell lung cancer
Authors: Sculier J-P. , Moro-Sibilot D.
Published: March 2009

The objectives for the treatment of advanced nonsmall cell lung cancer are palliative and include improvement of survival, symptom control, quality of life and cost. The level of evidence of these benefits is based on multiple randomised trials and meta-analyses. Cisplatin-based chemotherapy with one of the regimens shown to be effective should be preferred. Carboplatin may be substituted for cisplatin if medical contraindications exist. Nonplatinum-based regimens are indicated as first-line treatment for advanced nonsmall cell lung cancer in patients for whom platinum-based chemotherapy is contraindicated. Single drug chemotherapy may be considered in patients with poor performance status. The choice of the active drugs depends on the patient's medical condition. There is no conclusive evidence that high doses of cisplatin (100–120 mg·m−2) provide better results than standard lower doses (50–60 mg·m−2) in terms of survival. The optimal duration of chemotherapy is poorly documented in advanced nonsmall cell lung cancer. A minimum of four to six cycles is advised in responding patients. Second-line chemotherapy is now accepted as a standard and should be offered to patients with good performance status and failing platinum-based first-line chemotherapy. Evidence is in favour of docetaxel and in the case of adenocarcinoma and adequate renal function, pemetrexed is recommended.
Mimitin – a novel cytokine-regulated mitochondrial protein
Authors: Wegrzyn Paulina , Yarwood Stephen J , Fiegler Nathalie , Bzowska Monika , Koj Aleksander , Mizgalska Danuta , Malicki Stanisław , Pajak Magdalena , Kasza Aneta , Kachamakova-Trojanowska Neli , Bereta Joanna , Jura Jacek , Jura Jolanta
Published: March 2009

Background

The product of a novel cytokine-responsive gene discovered by differential display analysis in our earlier studies on HepG2 cells was identified as mimitin – a small mitochondrial protein. Since proinflammatory cytokines are known to affect components of the respiratory chain in mitochondria, and mimitin was reported as a possible chaperone for assembly of mitochondrial complex I, we looked for the effects of modulation of mimitin expression and for mimitin-binding partners.

Results

By blocking mimitin expression in HepG2 cells by siRNA we found that mimitin has no direct influence on caspase 3/7 activities implicated in apoptosis. However, when apoptosis was induced by TNF and cycloheximide, and mimitin expression blocked, the activities of these caspases were significantly increased. This was accompanied by a slight decrease in proliferation of HepG2 cells. Our observations suggest that mimitin may be involved in the control of apoptosis indirectly, through another protein, or proteins. Using the yeast two-hybrid system and coimmunoprecipitation we found MAP1S among proteins interacting with mimitin. MAP1S is a recently identified member of the microtubule-associated protein family and has been shown to interact with NADH dehydrogenase I and cytochrome oxidase I. Moreover, it was implicated in the process of mitochondrial aggregation and nuclear genome destruction. The expression of mimitin is stimulated more than 1.6-fold by IL-1 and by IL-6, with the maximum level of mimitin observed after 18–24 h exposure to these cytokines. We also found that the cytokine-induced signal leading to stimulation of mimitin synthesis utilizes the MAP kinase pathway.

Conclusion

Mimitin is a mitochondrial protein upregulated by proinflammatory cytokines at the transcriptional and protein levels, with MAP kinases involved in IL-1-dependent induction. Mimitin interacts with a microtubular protein (MAP1S), and some changes of mimitin gene expression modulate activity of apoptotic caspases 3/7, suggesting that this protein may indirectly participate in apoptosis.
Sequencing strategy for the whole mitochondrial genome resulting in high quality sequences
Authors: Fendt Liane , Zimmermann Bettina , Daniaux Martin , Parson Walther
Published: March 2009

Background

It has been demonstrated that a reliable and fail-safe sequencing strategy is mandatory for high-quality analysis of mitochondrial (mt) DNA, as the sequencing and base-calling process is prone to error. Here, we present a high quality, reliable and easy handling manual procedure for the sequencing of full mt genomes that is also appropriate for laboratories where fully automated processes are not available.

Results

We amplified whole mitochondrial genomes as two overlapping PCR-fragments comprising each about 8500 bases in length. We developed a set of 96 primers that can be applied to a (manual) 96 well-based technology, which resulted in at least double strand sequence coverage of the entire coding region (codR).

Conclusion

This elaborated sequencing strategy is straightforward and allows for an unambiguous sequence analysis and interpretation including sometimes challenging phenomena such as point and length heteroplasmy that are relevant for the investigation of forensic and clinical samples.
Adipogenic and energy metabolism gene networks in longissimus lumborum during rapid post-weaning growth in Angus and Angus × Simmental cattle fed high-starch or low-starch diets
Authors: Graugnard Daniel E , Piantoni Paola , Bionaz Massimo , Berger Larry L , Faulkner Dan B , Loor Juan J
Published: March 2009

Background

Transcriptional networks coordinate adipocyte differentiation and energy metabolism in rodents. The level of fiber and starch in diets with adequate energy content fed to young cattle has the potential to alter intramuscular adipose tissue development in skeletal muscle. Post-weaning alterations in gene expression networks driving adipogenesis, lipid filling, and intracellular energy metabolism provide a means to evaluate long-term effects of nutrition on longissimus muscle development across cattle types.

Results

Longissimus lumborum (LL) from Angus (n = 6) and Angus × Simmental (A × S; n = 6) steer calves (155 ± 10 days age) fed isonitrogenous high-starch (HiS; 1.43 Mcal/kg diet dry matter; n = 6) or low-starch (LoS; 1.19 Mcal/kg diet dry matter; n = 6) diets was biopsied at 0, 56, and 112 days of feeding for transcript profiling of 31 genes associated with aspects of adipogenesis and energy metabolism. Intake of dietary energy (9.44 ± 0.57 Mcal/d) across groups during the study did not differ but feed efficiency (weight gain/feed intake) during the first 56 days was greater for steers fed HiS. Expression of PPARG increased ca. 2-fold by day 56 primarily due to HiS in A × S steers. Several potential PPARG-target genes (e.g., ACACA, FASN, FABP4, SCD) increased 2.5-to-25-fold by day 56 across all groups, with responses (e.g., FASN, FABP4) being less pronounced in A × S steers fed LoS. This latter group of steers had markedly greater blood plasma glucose (0.99 vs. 0.79 g/L) and insulin (2.95 vs. 1.17 μg/L) by day 112, all of which were suggestive of insulin resistance. Interactions were observed for FABP4, FASN, GPAM, SCD, and DGAT2, such that feeding A × S steers high-starch and Angus steers low-starch resulted in greater fold-changes by day 56 or 112 (GPAM). Marked up-regulation of INSIG1 (4-to-8-fold) occurred throughout the study across all groups. SREBF1 expression, however, was only greater on day 112 namely due to LoS in A × S steers. The lipogenic transcription factor THRSP was 6-to-60-fold greater by day 56 primarily due to HiS in A × S steers, constituting the greatest response among all genes.

Conclusion

Results involving gene markers of mature adipocytes (e.g., PPARG, THRSP, SCD) provided evidence of intramuscular adipose tissue differentiation during the early portion of the growing phase. The resulting gene networks underscored a central role for PPARG in controlling transcription of genes which are known to co-ordinately regulate adipocyte differentiation and lipid filling in non-ruminants. Unlike rodents, INSIG1 appears to play an important role in cattle muscle adipogenesis. We propose that a network of transcription regulators and nuclear receptors including PPARG-target genes, INSIG1, and THRSP, coordinate activation of adipocyte differentiation and lipid filling at an early age.
Significant difference between three observers in the assessment of intraepidermal nerve fiber density in skin biopsy
Authors: Wöpking Sigrid , Scherens Andrea , Haußleiter Ida S , Richter Helmut , Schüning Julia , Klauenberg Sabrina , Maier Christoph
Published: March 2009

Background

The determination of Intraepidermal Nerve Fiber Density (IENFD) in skin biopsy is a useful method for the evaluation of different types of peripheral neuropathies. To allow a reliable use of the method it is necessary to determine interobserver reliability. Previous studies dealing with this topic used limited suitable statistical methods.

Methods

In the present study three observers determined the IENFD and estimated the staining quality of the basement membrane for an adequate quantity of 120 skin biopsies (stained with indirect immunofluorescence technique) from 68 patients. More adequate statistical methods like intraclass correlation coefficient and Bland Altman Plot were chosen to estimate interobserver reliability.

Results

We found an unexpected significant difference in IENFD between the observers (p < 0.05) and so the results of this study are not in line with the high interobserver reliability reported before (intraclass correlation coefficient: 0.73). The Bland Altmann Plot showed a variance growing with rising mean. The difference in IENFD between the observers and the resulting low interobserver reliability is likely caused by different interpretations of the standard counting rules. There was no significant difference in IENFD between observers for biopsies with a well-defined basement membrane. Thus skin biopsies with an inexactly defined basement membrane should not be used diagnostically for the determination of IENFD.

Conclusion

These results emphasise that standardisation of the method is extremely important and at least two observers should analyse skin biopsies with critical IENFD near the cut-off values.
Anopheles pseudowillmori is the predominant malaria vector in Motuo County, Tibet Autonomous Region
Authors: Song Wu , Jia-Yun Pan , Xue-Zhong Wang , Shui-Sen Zhou , Guo-Qing Zhang , Qian Liu , Lin-Hua Tang
Published: March 2009

Background

Malaria is endemic in Linzhi Prefecture in the Tibet Autonomous Region (TAR), but the vector for malaria transmission had never been identified.

Methods

Adult Anopheles spp. were collected in Motuo County, Linzhi Prefecture on the Sino-Indian border in July and August, 2007. Multiplex PCR was adopted for species identification, and a nested PCR approach was used to detect sporozoites in the salivary glands of the mosquitoes.

Results

3,675 mosquitoes of the Anopheles maculatus group were collected and processed for species identification. Among them, 3,602 (98.0%) were Anopheles pseudowillmori and 73 (2.0%) were Anopheles willmori. The Plasmodium vivax SSUrDNA fragment was amplified in two of 360 pooled An. pseudowillmori samples.

Conclusion

The local An. maculatus group comprises the species An. pseudowillmori and An. willmori. Anopheles pseudowillmori is considered the sole malaria vector in Motuo County in Linzhi Prefecture.
Multifactor dimensionality reduction analysis identifies specific nucleotide patterns promoting genetic polymorphisms
Authors: Arehart Eric , Gleim Scott , White Bill , Hwa John , Moore Jason H
Published: March 2009

Background

The fidelity of DNA replication serves as the nidus for both genetic evolution and genomic instability fostering disease. Single nucleotide polymorphisms (SNPs) constitute greater than 80% of the genetic variation between individuals. A new theory regarding DNA replication fidelity has emerged in which selectivity is governed by base-pair geometry through interactions between the selected nucleotide, the complementary strand, and the polymerase active site. We hypothesize that specific nucleotide combinations in the flanking regions of SNP fragments are associated with mutation.

Results

We modeled the relationship between DNA sequence and observed polymorphisms using the novel multifactor dimensionality reduction (MDR) approach. MDR was originally developed to detect synergistic interactions between multiple SNPs that are predictive of disease susceptibility. We initially assembled data from the Broad Institute as a pilot test for the hypothesis that flanking region patterns associate with mutagenesis (n = 2194). We then confirmed and expanded our inquiry with human SNPs within coding regions and their flanking sequences collected from the National Center for Biotechnology Information (NCBI) database (n = 29967) and a control set of sequences (coding region) not associated with SNP sites randomly selected from the NCBI database (n = 29967). We discovered seven flanking region pattern associations in the Broad dataset which reached a minimum significance level ofp≤ 0.05. Significant models (p<< 0.001) were detected for each SNP type examined in the larger NCBI dataset. Importantly, the flanking region models were elongated or truncated depending on the nucleotide change. Additionally, nucleotide distributions differed significantly at motif sites relative to the type of variation observed. The MDR approach effectively discerned specific sites within the flanking regions of observed SNPs and their respective identities, supporting the collective contribution of these sites to SNP genesis.

Conclusion

The present study represents the first use of this computational methodology for modeling nonlinear patterns in molecular genetics. MDR was able to identify distinct nucleotide patterning around sites of mutations dependent upon the observed nucleotide change. We discovered one flanking region set that included five nucleotides clustered around a specific type of SNP site. Based on the strongly associated patterns identified in this study, it may become possible to scan genomic databases for such clustering of nucleotides in order to predict likely sites of future SNPs, and even the type of polymorphism most likely to occur.
Prevention of first-episode depression: progress and potential
Authors: Robinson Robert G. , Jorge Ricardo E.
Published: March 2009

Preventive intervention for first-episode depression is an exciting, emerging field. Many questions remain, however. Should we target patients who have sub-syndromal symptom elevations (i.e. indicated intervention) or should we intervene in high-risk groups (i.e. selective intervention)? Furthermore, should primary outcomes be incident depressions or long-term decreases in morbidity or mortality?
A manualised in-patient programme for young people with anorexia based on NICE guidance
Authors: Rous Elizabeth , Ranote Sandeep , Elvins Rachel , Bhatt Asha
Published: March 2009

Aims and Method

The Rainbow programme was introduced in January 2004 as a structured in-patient treatment for anorexia. There were two strands to the programme evaluation: a notes review of a cohort of in-patients and a series of questionnaires to users, carers and staff.

Results

There was an improvement in adherence to the National Institute for Health and Clinical Excellence guidelines and 94% of staff responders found the Rainbow programme framework useful.

Clinical Implications

The Rainbow programme improved the level of care provided. There is scope for improvement in the distribution of the programme manual.
Use and perceived utility of structured violence risk assessments in English medium secure forensic units
Authors: Khiroya Reena , Weaver Tim , Maden Tony
Published: March 2009

Aims and Method

We surveyed the usage and perceived utility of standardised risk measures in 29 forensic medium secure units (a 62% response rate).

Results

The most common instruments were Historical Clinical Risk–20 (HCR–20) and Psychopathy Checklist – revised (PCL–R); both were rated highly for utility. the Risk Matrix 2000 (RM2000), Sex Offender Risk Appraisal Guide (SORAG) and Static-99 were the most common sex offender assessments, but the Sexual Violence Risks–20 (SVR–20) was rated more positively for its use of dynamic factors and relevance to treatment.

Clinical Implications

Most medium secure units use structured risk assessments and staff view them positively. As HCR–20 and PCL–R/PCL–SV (Psychopathy Checklist – Screening Version) are so widely used they should be the first choices considered by other services.
Multi-agency working: challenges in getting it right
Authors: Coccia Floriana , Robertson Kate
Published: March 2009

Aims and Method

Multidisciplinary approaches to complex cases referred to child and adolescent mental health services (CAMHS) are both mandated and necessary. However, multidisciplinary working is time-consuming and resource-intensive, especially where processes are not functioning optimally. We describe a completed audit cycle: auditing the consultation and liaison service within a community CAMHS, introducing service modifications and repeating the audit 6 months later.

Results

During the first audit over 80% of data were lost; in the re-audit only 30% were lost. Audit results were successfully used to stimulate, design and implement change, with service improvement.

Clinical Implications

Auditing the process of interdisciplinary consultations is challenging, but possible. Where staff seek service improvement, audit can result in positive change without alienating staff.
Cytokeratin-19 mRNA-Positive Circulating Tumor Cells After Adjuvant Chemotherapy in Patients With Early Breast Cancer
Authors: Xenidis Nikolaos , Ignatiadis Michail , Apostolaki Stella , Perraki Maria , Kalbakis Kostas , Agelaki Sofia , Stathopoulos Efstathios N. , Chlouverakis Grigorios , Lianidou Evi , Kakolyris Stylianos , Georgoulias Vassilis , Mavroudis Dimitris
Published: March 2009

Purpose

To evaluate the prognostic significance of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in peripheral blood of women with early-stage breast cancer after the completion of adjuvant chemotherapy.

Patients and Methods

Blood was obtained from 437 patients with early breast cancer before the start and after the completion of adjuvant chemotherapy, and the presence of CK-19 mRNA-positive CTCs was assessed by real-time reverse transcriptase polymerase chain reaction. Interaction with known prognostic factors and association of CTCs with clinical outcome were investigated.

Results

CK-19 mRNA-positive CTCs were detected before chemotherapy in 179 patients (41.0%). After adjuvant chemotherapy, a significant change in CK-19 status was observed, as status for 51% of patients with initially CK-19 mRNA-positive disease turned negative, and status for 22% of patients with initially CK-19 mRNA-negative disease became positive (McNemar test P = .004). The detection of CK-19 mRNA-positive CTCs postchemotherapy was associated with involvement of more than three axillary lymph nodes (P = .026). Clinical relapses and disease-related deaths were significantly increased in patients with detectable postchemotherapy CK-19 mRNA-positive CTCs (both P < .001, respectively). Disease-free and overall survival were significantly reduced in patients with detectable CK-19 mRNA-positive CTCs postchemotherapy (P < .001 and P = .001, respectively). In multivariate analysis, the detection of CK-19 mRNA-positive CTCs before and after adjuvant chemotherapy was an independent factor associated with reduced disease-free survival (P < .001) and overall survival (P = .003).

Conclusion

The detection of CK-19 mRNA-positive CTCs in the blood after adjuvant chemotherapy is an independent risk factor indicating the presence of chemotherapy-resistant residual disease.
Strategic Planning with Start-Time Dependent Variable Costs
Authors: Luedtke James , Nemhauser George L.
Published: March 2009

We present a strategic planning model in which the activities to be planned, such as production and distribution in a supply network, require technology to be installed before they can be performed. The technology improves over time, so that a decision maker has incentive to delay starting an activity to take advantage of better technology and lower operational costs. The model captures the fundamental trade-off between delaying the start time of an activity and the need for some activities to be performed now. Models of this type are used in the oil industry to plan the development of oil fields. This problem is naturally formulated as a mixed-integer program with a bilinear objective. We develop a series of progressively more compact mixed-integer linear formulations, along with classes of valid inequalities that make the formulations strong. We also present a specialized branch-and-cut algorithm to solve an extremely compact concave formulation. Computational results indicate that these formulations can be used to solve large-scale instances, whereas a straightforward linearization of the mixed-integer bilinear formulation fails to solve even small instances.
Design for Process Flexibility: Efficiency of the Long Chain and Sparse Structure
Authors: Chou Mabel C. , Chua Geoffrey A. , Teo Chung-Piaw , Zheng Huan
Published: March 2009

The concept of chaining, or in more general terms, sparse process structure, has been extremely influential in the process flexibility area, with many large automakers already making this the cornerstone of their business strategies to remain competitive in the industry. The effectiveness of the process strategy, using chains or other sparse structures, has been validated in numerous empirical studies. However, to the best of our knowledge, there have been relatively few concrete analytical results on the performance of such strategies vis-á-vis the full flexibility system, especially when the system size is large or when the demand and supply are asymmetrical. This paper is an attempt to bridge this gap.

We study the problem from two angles: (1) For the symmetrical system where the (mean) demand and plant capacity are balanced and identical, we utilize the concept of a generalized random walk to evaluate the asymptotic performance of the chaining structure in this environment. We show that a simple chaining structure performs surprisingly well for a variety of realistic demand distributions, even when the system size is large. (2) For the more general problem, we identify a class of conditions under which only a sparse flexible structure is needed so that the expected performance is already within ϵ optimality of the full flexibility system.

Our approach provides a theoretical justification for the widely held maxim: In many practical situations, adding a small number of links to the process flexibility structure can significantly enhance the ability of the system to match (fixed) production capacity with (random) demand.
New trends and techniques in open reduction and internal fixation of fractures of the tibial plateau
Authors: Musahl V. , Tarkin I. , Kobbe P. , Tzioupis C. , Siska P. A. , Pape H.-C.
Published: March 2009

The operative treatment of displaced fractures of the tibial plateau is challenging. Recent developments in the techniques of internal fixation, including the development of locked plating and minimal invasive techniques have changed the treatment of these fractures. We review current surgical approaches and techniques, improved devices for internal fixation and the clinical outcome after utilisation of new methods for locked plating.
A lateral approach to the distal humerus following identification of the cutaneous branches of the radial nerve
Authors: Hannouche D. , Ballis R. , Raould A. , Nizard R. S. , Masquelet A. C.
Published: March 2009

We describe a lateral approach to the distal humerus based on initial location of the superficial branches of the radial nerve, the inferior lateral cutaneous nerve of the arm and the posterior cutaneous nerve of the forearm. In 18 upper limbs the superficial branches of the radial nerve were located in the subcutaneous tissue between the triceps and brachioradialis muscles and dissected proximally to their origin from the radial nerve, exposing the shaft of the humerus. The inferior lateral cutaneous nerve of the arm arose from the radial nerve at the lower part of the spiral groove, at a mean of 14.2 cm proximal to the lateral epicondyle. The posterior cutaneous nerve of the forearm arose from the inferior lateral cutaneous nerve at a mean of 6.9 cm (6.0 to 8.1) proximal to the lateral epicondyle and descended vertically along the dorsal aspect of the forearm. The size and constant site of emergence between the triceps and brachioradialis muscles constitute a readily identifiable landmark to explore the radial nerve and expose the humeral shaft.
Is a valgus position of the femoral component in hip resurfacing protective against spontaneous fracture of the femoral neck?
Authors: Schnurr C. , Nessler J. , Meyer C. , Schild H. H. , Koebke J. , König D. P.
Published: March 2009

The aim of our study was to investigate whether placing of the femoral component of a hip resurfacing in valgus protected against spontaneous fracture of the femoral neck.

We performed a hip resurfacing in 20 pairs of embalmed femora. The femoral component was implanted at the natural neck-shaft angle in the left femur and with a 10° valgus angle on the right. The bone mineral density of each femur was measured and CT was performed. Each femur was evaluated in a materials testing machine using increasing cyclical loads.

In specimens with good bone quality, the 10° valgus placement of the femoral component had a protective effect against fractures of the femoral neck. An adverse effect was detected in osteoporotic specimens.

When resurfacing the hip a valgus position of the femoral component should be achieved in order to prevent fracture of the femoral neck. Patient selection remains absolutely imperative. In borderline cases, measurement of bone mineral density may be indicated.
Chronic diabetic ulcers under the first metatarsal head treated by staged tendon balancing
Authors: Dayer R. , Assal M.
Published: March 2009

We studied a cohort of 26 diabetic patients with chronic ulceration under the first metatarsal head treated by a modified Jones extensor hallucis longus and a flexor hallucis longus transfer. If the first metatarsal was still plantar flexed following these two transfers, a peroneus longus to the peroneus brevis tendon transfer was also performed. Finally, if ankle dorsiflexion was < 5° with the knee extended, a Strayer-type gastrocnemius recession was performed.

The mean duration of chronic ulceration despite a minimum of six months’ conservative care was 16.2 months (6 to 31). A total of 23 of the 26 patients were available for follow-up at a mean of 39.6 months (12 to 61) after surgery. All except one achieved complete ulcer healing at a mean of 4.4 weeks (2 to 8) after surgery, and there was no recurrence of ulceration under the first metatarsal.

We believe that tendon balancing using modified Jones extensor hallucis longus and flexor hallucis longus transfers, associated in selected cases with a peroneus longus to brevis transfer and/or Strayer procedure, can promote rapid and sustained healing of chronic diabetic ulcers under the first metatarsal head.
The intra-operative joint gap in cruciate-retaining compared with posterior-stabilised total knee replacement
Authors: Matsumoto T. , Kuroda R. , Kubo S. , Muratsu H. , Mizuno K. , Kurosaka M.
Published: March 2009

We have developed a new tensor for total knee replacements which is designed to assist with soft-tissue balancing throughout the full range of movement with a reduced patellofemoral joint. Using this tensor in 40 patients with osteoarthritis we compared the intra-operative joint gap in cruciate-retaining and posterior-stabilised total knee replacements at 0°, 10°, 45°, 90° and 135° of flexion, with the patella both everted and reduced.

While the measurement of the joint gap with a reduced patella in posterior-stabilised knees increased from extension to flexion, it remained constant for cruciate-retaining joints throughout a full range of movement. The joint gaps at deep knee flexion were significantly smaller for both types of prosthetic knee when the patellofemoral joint was reduced (p < 0.05).
The Thomas splint
Authors: Robinson P. M. , O’Meara M. J.
Published: March 2009

The Thomas splint is a common piece of equipment in emergency departments and orthopaedic units in hospitals worldwide. Its basic design has changed little since its first description by Hugh Owen Thomas was published in 1875. We have reviewed the origins of the Thomas splint as a means of correction of deformities of the lower limb and its evolution through both World Wars into an essential item for the management of trauma of the lower limb.
Galectin-3 Overexpression in Invasive Laryngeal Carcinoma, Assessed by Computer-assisted Analysis
Authors: Miranda Fabiana A. , Hassumi Marcela K. , Guimarães Marcia C.M. , Simões Renata T. , Silva Tarsia G.A. , Lira Régia C.P. , Rocha Ana M. , Mendes Celso T. , Donadi Eduardo A. , Soares Christiane P. , Soares Edson G.
Published: March 2009

The larynx is the most common site of malignancy in the upper aerodigestive tract. In Brazil, malignant laryngeal lesions represent 2% of all cancers, with ∼3000 annual deaths. The association between human papillomavirus (HPV) and laryngeal cancer is still controversial. The aim of the present retrospective study was to determine the expression of galectin-3 immunoperoxidase in laryngeal carcinoma by examining paraffin-embedded larynx biopsies from 65 patients, 10 in situ laryngeal carcinomas, 27 laryngeal carcinomas without metastases, and 28 with metastases. Twenty-eight cervical lymph nodes from patients with metastatic lesions were also evaluated. Nested PCR was performed to detect and type HPV DNA. Galectin-3 expression was assessed by immunohistochemistry using a computer-assisted system. Among 65 patients, 55 (84.6%) were positive to beta-globin (internal control); 10 (15.4%) patients were beta-globin negative and were excluded from the HPV evaluation. Thus, 7 (12.7%) out of 55 patients were HPV positive and 48 (87.3%) out of 55 patients were HPV negative. High expression of galectin-3 was observed in invasive laryngeal tumors, suggesting that galectin-3 could be associated with the invasiveness and aggressiveness of laryngeal carcinomas. (J Histochem Cytochem 57:665–673, 2009)
Quantitative In Situ Detection of Phosphoproteins in Fixed Tissues Using Quantum Dot Technology
Authors: Bodo Juraj , Durkin Lisa , Hsi Eric D.
Published: March 2009

Detection and quantitation of phosphoproteins (PPs) in fixed tissues will become increasingly important as additional inhibitors of protein kinases enter clinical use and new disease entities are defined by molecular changes affecting PP levels. We characterize fixation conditions suitable for accurate PP quantitation that are achievable in a clinical laboratory and illustrate the utility of in situ quantitation of PPs by quantum dot (QD) nano-crystals in two models: (1) a therapeutic model demonstrating effects of a targeted therapeutic (quantitative reduction of phospho-GSK3β) in xenografts treated with enzas-taurin; and (2) a diagnostic model that identifies elevated levels of nuclear phospho-STAT5 in routine bone marrow biopsies from patients with acute myeloid leukemia based on the presence of the activating FLT3-ITD mutation. Finally, we document production of a well-characterized tissue microarray of widely available cell lines as a multilevel calibrator for validating numerous phosphoprotein assays. QD immunofluorescence is an ideal method for in situ quantitation of PPs in fixed samples, providing valuable cell type—specific and subcellular information about pathway activation in primary tissues. (J Histochem Cytochem 57:701–708, 2009)
A Genetic Analysis of Coffee Consumption in a Sample of Dutch Twins
Authors: Vink Jaqueline M. , Staphorsius Annemieke S. , Boomsma Dorret I.
Published: March 2009

Caffeine is by far the most commonly used psychoactive substance. Caffeine is consumed regularly as an ingredient of coffee. Coffee consumption and coffee preference was explored in a sample of 4,495 twins (including 1,231 pairs) registered with the Netherlands Twin Registry. Twin resemblance was assessed by tetrachoric correlations and the influence of both genetic and environmental factors was explored with model fitting analysis in MX. Results showed moderate genetic influences (39%) on coffee consumption. The remaining variance was explained by shared environmental factors (21%) and unique environmental factors (40%). The variance in coffee preference (defined as the proportion of coffee consumption relative to the consumption of coffee and tea in total) was explained by genetic factors (62%) and unique environmental factors (38%).
A Web-Based Study of Personality, Psychopathology and Substance Use in Twin, Other Relative and Relationship Pairs
Authors: Kendler Kenneth S. , Myers John , Potter Jeff , Opalesky Jill
Published: March 2009

Web-based studies have become increasingly common in the social sciences, but have been rare in genetic epidemiology in general and twin studies in particular. We here review the methods, validity checks and preliminary correlational data from an on-line questionnaire collected from 2005–2008. During this time period, 44,112 individuals completed the questionnaire. This sample was 65.3% female, 85.4% 18 years or older, 72.0% Caucasian and had a mean educational level of 12.2 years. The sample included 609 twin, 333 sibling and 201 parent-offspring pairs as well as 342 dating partners, 313 ‘significant other’ pairs, 327 spouses and 2,316 friend pairs. A range of checks suggested low levels of invalid data. Correlations for personality, substance use and misuse, lifetime major depression, social attitudes, educational status, and height and weight were broadly similar to those obtained previously using conventional assessment methods. Web-based studies are a relatively easy and inexpensive way to ascertain large numbers of individuals, although obtaining twin pairs is more difficult, and female and monozygotic pairs are overrepresented. The sample is diverse and pair resemblance is generally similar to that obtained using interviews or mailed questionnaires.
On the History of Hellin's Law
Authors: Fellman Johan , Eriksson Aldur W.
Published: March 2009

Theorems, proofs, laws and rules are commonly named according to the presumed investigator, but often earlier investigators have contributed substantially to the findings. One example of this is Hellin's law, which was named after Hellin, although he was not the first to discover it. In research on twinning and higher multiple maternities, the law has played a central role because it is approximately correct, despite showing discrepancies that are difficult to explain or eliminate. Several improvements to this law have been proposed. In this study, we re-examine some old papers to provide an overview of the scientists who have contributed to the genesis and the improvements of this law. In addition, we consider more recent contributions in which Hellin's law has been discussed and evaluated. It has been mathematically proven that Hellin's law does not hold as a general rule. However, most studies are based on empirical rates of multiple maternities, ignoring random errors. Such studies can never confirm the law, but only serve to identify errors too large to be characterized as random.
Optimum Strategies to Reduce Residual Stresses and Distortion during the Metal Quenching Process
Authors: Nallathambi Ashok Kumar , Kaymak Yalcin , Specht Eckehard , Bertram Albrecht
Published: March 2009

Quenching is a complex thermo-mechano-metallurgical problem. Unexplored or without an optimized cooling strategy, a quenching process can end up with high residual stresses and distortion. This paper presents the mathematical formulation of the physics behind the quenching process, the numerical technique and optimization of the cooling strategies for the selected geometries. The finite element method (FEM) is used to solve the coupled partial differential equations in the framework of an isothermal-staggered approach. The solid-solid phase transformations are modeled using a linear iso-kinetic law with Schiel’s additivity rule and Koistinen-Marburger (KM) law. The thermoplastic material model is formulated on the basis of J2-plasticity theory with a temperature and phase fraction-dependent yield limit together with the appropriate mixture rule. The coupling effects such as phase transformation enthalpy, transformation-induced plasticity and dissipation are considered. The local heat transfer coefficient (HTC) during the quenching process plays a crucial role for the evolution of the distortion and residual stresses. It is demonstrated that with an enhanced quenching at the mass lumped regions, the distortion can be reduced. It is always possible to find an HTC profile which eliminates the distortion completely on the expense of an increased residual stress state. Therefore, an optimum quenching strategy has to be found to reduce the distortion and the residual stresses simultaneously. It is shown that with an enhanced quenching at the mass lumped regions and with a reduced quenching at the edges and corners, stresses and distortion can be minimized simultaneously. Examples are given for different kinds of metals and geometries such as long profiles (L and T) and disk with a hole.