bluuebunny/crossref_metadata_2025 huggingface dataset:
New Perspectives on Ethiopian and African Christianity: Communalities and Contrasts in Twentieth Century Religious Experience
Authors: Persoon Joachim
Published: November 2005

Recent political developments and factors within Ethiopian studies have led to more emphasis on the African rather than Semitic elements in Ethiopian Culture. In the religious sphere likewise there are striking communalities in the 20th century experience of Ethiopian and wider African Christendom. Some of these can be ascribed to sharing similar sociological conditions i.e. religious resurgence as a response to the marginalisation and poverty associated with globalisation. However, resemblance between Ethiopian traditions and recently developed African Christian 'traditions' indicate more profound communalities in religious perception. The paradigm of the 'knowledge buffet' and the relationship between food and religion is developed into a scheme of three stages or courses in the evolution of African and Ethiopian Christendom. These are characterised by institutionalisation, indigenisation, and internationalisation. This exemplifies the interaction between global and local factors, as individuals seek empowerment and the transformation of a negative life world through the development of religious discourse.
Mission for the Practice of Auction in the Batak Church in Indonesia
Authors: Sihombing Batara
Published: November 2005

For the sake of its mission the church needs to have funds. Auction is used by the Batak church in Indonesia to raise fund-rising. Normally, it is carried out at the time of church festival. The competitiveness of the Batak feature seems to suit the spirit of auction. Even though the practice of auction could collect money for the church, it also brings about some weaknesses for the Batak church to grow.
Numerical Simulation of Katabatic Flow with Changing Slope Angle
Authors: Smith Craig M. , Skyllingstad Eric D.
Published: November 2005

A large eddy simulation (LES) model and the Advanced Regional Prediction System (ARPS) model, which does not resolve turbulent eddies, are used to study the effect of a slope angle decrease on the structure of katabatic slope flows. For a simple, uniform angle slope, simulations from both models produce turbulence kinetic energy and momentum budgets that are in good overall agreement. Simulations of a compound angle slope are compared to a uniform angle slope to demonstrate how a changing slope angle can strongly affect the strength of katabatic flows. Both ARPS and the LES model show that slopes with a steep upper slope followed by a shallower lower slope (concave shape) generate a rapid acceleration on the upper slope followed by a transition to a slower evolving structure characterized by an elevated jet over the lower slope. In contrast, the case with uniform slope (having the same total height change) yields a more uniform flow profile with stronger winds at the slope bottom. Higher average slope in the uniform slope angle case generates greater gravitational potential energy, which is converted to kinetic energy at the bottom of the slope. Analysis of the total energy budget of slope flows indicates a consistent structure where potential energy generated at the top of the slope is transported downslope and converted into kinetic energy near the slope base.
The Alpine Mountain–Plain Circulation: Airborne Doppler Lidar Measurements and Numerical Simulations
Authors: Weissmann M. , Braun F. J. , Gantner L. , Mayr G. J. , Rahm S. , Reitebuch O.
Published: November 2005

On summer days radiative heating of the Alps produces rising air above the mountains and a resulting inflow of air from the foreland. This leads to a horizontal transport of air from the foreland to the Alps, and a vertical transport from the boundary layer into the free troposphere above the mountains. The structure and the transports of this mountain–plain circulation in southern Germany (“Alpine pumping”) were investigated using an airborne 2-μm scanning Doppler lidar, a wind-temperature radar, dropsondes, rawinsondes, and numerical models. The measurements were part of the Vertical Transport and Orography (VERTIKATOR) campaign in summer 2002. Comparisons of dropsonde and lidar data proved that the lidar is capable of measuring the wind direction and wind speed of this weak flow toward the Alps (1–4 m s−1). The flow was up to 1500 m deep, and it extended ∼80 km into the Alpine foreland. Lidar data are volume measurements (horizontal resolution ∼5 km, vertical resolution 100 m). Therefore, they are ideal for the investigation of the flow structure and the comparison to numerical models. Even the vertical velocities measured by the lidar agreed with the mass budget calculations in terms of both sign and magnitude. The numerical simulations with the fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5) (mesh size 2 and 6 km) and the Local Model (LM) of the German Weather Service (mesh size 2.8 and 7 km) reproduced the general flow structure and the mass fluxes toward the Alps within 86%–144% of the observations.
A Comparison between the 4DVAR and the Ensemble Kalman Filter Techniques for Radar Data Assimilation
Authors: Caya A. , Sun J. , Snyder C.
Published: November 2005

A four-dimensional variational data assimilation (4DVAR) algorithm is compared to an ensemble Kalman filter (EnKF) for the assimilation of radar data at the convective scale. Using a cloud-resolving model, simulated, imperfect radar observations of a supercell storm are assimilated under the assumption of a perfect forecast model. Overall, both assimilation schemes perform well and are able to recover the supercell with comparable accuracy, given radial-velocity and reflectivity observations where rain was present. 4DVAR produces generally better analyses than the EnKF given observations limited to a period of 10 min (or three volume scans), particularly for the wind components. In contrast, the EnKF typically produces better analyses than 4DVAR after several assimilation cycles, especially for model variables not functionally related to the observations. The advantages of the EnKF in later cycles arise at least in part from the fact that the 4DVAR scheme implemented here does not use a forecast from a previous cycle as background or evolve its error covariance. Possible reasons for the initial advantage of 4DVAR are deficiencies in the initial ensemble used by the EnKF, the temporal smoothness constraint used in 4DVAR, and nonlinearities in the evolution of forecast errors over the assimilation window.
Seven Risks Emerging From Life Patents and Corporate Science
Authors: Ekberg Merryn
Published: November 2005

This article examines some of the controversial issues emerging from the privatization of biomedical research and commercialization of biotechnology. The aim is to identify the dominant social, political, and ethical risks associated with the recent shift from academic to corporate science and from the increasing emphasis on investing in research projects that will result in the award of a monopoly patent. Identifying these risks may ultimately assist policy makers in designing new policies or reforming existing practices that will come closer to achieving an equitable balance between science pursued for the advance of knowledge and science pursued for patents and profit. The discussion may also assist the research directors or managers of biopharmaceutical companies in designing corporate policies that will optimize the balance between the serendipity of scientific discovery and the discipline of strategic business planning.
Government Technology Acquisition Policy: The Case of Proprietary Versus Open Source Software
Authors: Hemphill Thomas A.
Published: November 2005

This article begins by explaining the concepts of proprietary and open source software technology, which are now competing in the marketplace. A review of recent individual and cooperative technology development and public policy advocacy efforts, by both proponents of open source software and advocates of proprietary software, subsequently follows, with supporting positions articulated. This is followed by an analysis of the results of a recent draft of a Center for Strategic & International Studies global study of government initiatives to incorporate open source software as an option in their institutional operations. The article concludes with analysis and recommendations on public policies for appropriate software technology assessment policy. For governments, the encouragement of neutral standards (i.e., not favoring one software business model), open competition for research funding of software development, and nondiscrimination in computer software procurement policies will result in the most effective and efficient procurement decisions.
A Failing Grade for WEEE Take-Back Programs for Information Technology Equipment
Authors: Nakajima Nina , Vanderburg Willem H.
Published: November 2005

Product take-back (also called extended producer responsibility) has become a trend for dealing with the garbage resulting from categories of problematic products. Waste electrical and electronic equipment (WEEE) is one such category with computer equipment being of particular significance. This article provides a description of the European Union’s program to require the take-back of WEEE as well as the status of similar programs in Canada and the United States. It is concluded that although these programs meet the goal of reducing the quantity of hazardous materials going to landfills, they do not go to the root of the problem by means of preventive approaches that create more circular materials flows. Plastics used in WEEE pose a serious problem, as they are generally not recycled.
Importance of Femoral Tunnel Placement in Double-Bundle Posterior Cruciate Ligament Reconstruction
Authors: Petersen Wolf , Lenschow Simon , Weimann Andre , Strobel Michael J. , Raschke Michael J. , Zantop Thore
Published: November 2005

Background

Previous studies have identified the femoral attachment of the posterior cruciate ligament fibers as one of the primary determinants of fiber tension behavior. In addition, a double-bundle posterior cruciate ligament reconstruction has been shown to restore the intact knee kinematics more closely than does a single-bundle reconstruction.

Hypothesis

An anterior tunnel position in double-bundle posterior cruciate ligament reconstruction restores the biomechanics of the normal knee more closely than does a posterior tunnel position.

Study Design

Controlled laboratory study.

Methods

Kinematics and in situ forces of human knees after double-bundle posterior cruciate ligament reconstruction with 2 different femoral tunnel positions (anterior vs posterior) were evaluated using a robotic/universal force-moment sensor testing system. Within the same specimen, the resulting knee kinematics and in situ forces were compared. For statistical analysis, 2-way analysis of variance repeated measures were performed.

Results

The femoral tunnel position of the double-bundle hamstring graft had significant effect on the resulting posterior tibial displacement and in situ forces of the hamstring grafts. The anterior femoral tunnel position provided significantly less posterior tibial translation than did the posterior tunnel position. There was a tendency toward higher in situ forces of grafts fixed in the anterior tunnel when compared to the posterior position, but this difference was statistically not significant.

Conclusion

An anterior position of the bone tunnels in double-bundle posterior cruciate ligament reconstruction restores the normal knee kinematics more closely than does a posterior position of the tunnels.

Clinical Relevance

In double-bundle posterior cruciate ligament reconstruction, posterior placement of the tunnel should be avoided.
Anatomical Glenoid Reconstruction for Recurrent Anterior Glenohumeral Instability with Glenoid Deficiency Using an Autogenous Tricortical Iliac Crest Bone Graft
Authors: Warner Jon J. P. , Gill Thomas J. , O'Hollerhan James D. , Pathare Neil , Millett Peter J.
Published: November 2005

Background

Anterior shoulder instability associated with severe glenoid bone loss is rare, and little has been reported on this problem. Recent biomechanical and anatomical studies have suggested guidelines for bony reconstruction of the glenoid.

Hypothesis

Anatomical glenoid reconstruction will restore stability in shoulders with recurrent anterior instability owing to glenoid bone loss.

Study Design

Case series; Level of evidence, 4.

Methods

Eleven cases of traumatic recurrent anterior instability that required bony reconstruction for severe anterior glenoid bone loss were reviewed. In all cases, the length of the anterior glenoid defect exceeded the maximum anteroposterior radius of the glenoid based on preoperative assessment by 3-dimensional CT scan. Surgical reconstruction was performed using an intra-articular tricortical iliac crest bone graft contoured to reestablish the concavity and width of the glenoid. The graft was fixed with cannulated screws in combination with an anterior-inferior capsular repair.

Results

At mean follow-up of 33 months, the mean American Shoulder and Elbow Surgeons score was 94, compared with a preoperative score of 65. The University of California, Los Angeles score improved to 33 from 18. The Rowe score improved to 94 from a preoperative score of 28. The mean motion loss compared with the contralateral, normal shoulder was 7° of flexion, 14° of external rotation in abduction, and one spinous process level for internal rotation. All patients returned to preinjury levels of sport, and only 2 complained of mild pain with overhead sports activities. No patients reported any recurrent instability (dislocation or subluxation). The CT scans with 3-dimensional reconstructions obtained 4 to 6 months postoperatively demonstrated union of the bone graft with incorporation along the anterior glenoid rim and preservation of joint space.

Conclusion

Anatomical reconstruction of the glenoid with autogenous iliac crest bone graft for recurrent glenohumeral instability in the setting of bone deficiency is an effective form of treatment for this problem.
Ligamentous Posttraumatic Ankle Osteoarthritis
Authors: Valderrabano Victor , Hintermann Beat , Horisberger Monika , Fung Tak Shing
Published: November 2005

Background

Ankle sprains are the most common injuries in sports and recreational activities.

Hypothesis

Ankle osteoarthritis can be caused by ankle ligament lesions. Latency time between injury and osteoarthritis is influenced by the type and side of the injured ligaments. The side of the ligamentous lesion correlates with the hindfoot alignment.

Study Design

Case series; Level of evidence, 4.

Methods

Of a cohort of 247 patients with ankle arthritis, we reviewed data from 30 patients (33 ankles; mean age, 58.6 years) with ligamentous end-stage ankle osteoarthritis. The patients were evaluated etiologically, clinically, and radiologically.

Results

Etiologic analysis: 55% had a ligamentous lesion from sports injuries (soccer, 33%); 85% injured the lateral ankle ligaments, and 15% injured the medial and medial-lateral ligaments. The mean latency time between injury and osteoarthritis was 34.3 years. The survivorship rate for single severe ankle sprains was worse than that for chronic recurrent ligamentous lesions (mean latency time, 25.7 vs 38.0 years; P< .05), and the rate for medial sprains was worse than for lateral sprains (mean latency time, 27.5 vs 35.0 years; P< .05). At follow-up, the American Orthopaedic Foot and Ankle Society hindfoot score was 23.0 points, 52% had varus malalignment, 52% had persistent instability, and the mean ankle arthritis grade was 2.6 points. There was a correlation between chronic lateral ankle instability and varus malalignment.

Conclusion

Lateral ankle sprains in sports are the main cause of ligamentous posttraumatic ankle osteoarthritis and correlate with varus malalignment. At the time of end-stage ligamentous ankle osteoarthritis, persistent instability may be encountered.
Antecedent Biomarkers of Alzheimer’s Disease: The Adult Children Study
Authors: Coats Mary , Morris John C.
Published: November 2005

The Washington University Adult Children Study is a longitudinal study to develop and validate biological markers, imaging features, and other indicators of preclinical Alzheimer’s disease to aid in identifying individuals at high risk for developing symptomatic Alzheimer’s disease. Two groups of participants between the ages of 45 and 74 are being enrolled in the Adult Children Study. Group 1 represents adult children who have at least 1 parent with Alzheimer’s disease. Group 2 represents adult children whose parents have lived at least to age 70 without dementia. The Adult Children Study participants have been highly motivated to participate, and this study will require the investment of many years from the participants and the investigators before its most significant results will be known.
Horse madness (hippomania) and hippophobia
Authors: Papakostas Yiannis G. , Daras Michael D. , Liappas Ioannis A. , Markianos Manolis
Published: November 2005

Anthropophagic horses have been described in classical mythology. From a current perspective, two such instances are worth mentioning and describing: Glaucus of Potniae, King of Efyra, and Diomedes, King of Thrace, who were both devoured by their horses. In both cases, the horses’ extreme aggression and their subsequent anthropophagic behaviour were attributed to their madness (hippomania) induced by the custom of feeding them with flesh. The current problem of ‘mad cow’ disease (bovine spongiform encephalopathy) is apparently related to a similar feeding pattern. Aggressive behaviour in horses can be triggered by both biological and psychological factors. In the cases cited here, it is rather unlikely that the former were the cause. On the other hand, the multiple abuses imposed on the horses, coupled with peoples’ fantasies and largely unconscious fears (hippophobia), may possibly explain these mythological descriptions of the ‘horse-monsters’.
Old and mad in Victorian Oxford: a study of patients aged 60 and over admitted to the Warneford and Littlemore Asylums in the nineteenth century
Authors: Yorston Graeme , Haw Camilla
Published: November 2005

This is a historical case note analysis of older patients admitted to the Warneford and Littlemore Asylums in nineteenth-century Oxford. Of 1044 admissions to the Warneford, 93 patients were aged over 60 (8.9%). At Littlemore, 998 of a total of 5464 admissions were aged over 60 (18.3%). High levels of psychopathology were found, as in other studies examining patients of all ages, and were similar for the two institutions. The largest difference was in the death rate, which was much higher for Littlemore Asylum. This resulted from the preponderance of patients with organic diagnoses who were admitted to Littlemore, many of whom died shortly afterwards.
The Kramer-Pollnow syndrome: a contribution on the life and work of Franz Kramer and Hans Pollnow
Authors: Neumärker Klaus-Jürgen
Published: November 2005

In 1932 Franz Kramer (1878–1967) and Hans Pollnow (1902–43) described a hyperkinetic syndrome in children. Basically the symptoms described coincide with what is nowadays regarded as Attention Deficit Hyperactivity Disorder (ADHD) or Hyperkinetic syndrome. The authors of the study thus went down in the history of child and adolescent psychiatry with their eponymous Kramer-Pollnow syndrome, and have had a lasting influence on the development of the concepts relating to this topic. Both worked together at the psychiatric and neurological hospital at Berlin’s Charité under its head Karl Bonhoeffer, but as they were both Jewish they were forced to emigrate after the Nazis seized power. Until now, little has been known about their further fate and careers, so this study gives the first comprehensive account of their lives, based on documents found in the archives. It also presents an overview of their work.
Philosophy of mind in the Yogacara Buddhist idealistic school
Authors: Tola Fernando , Dragonetti Carmen
Published: November 2005

After some general introductory remarks on Indian philosophy, this essay deals with the structure of mind in the Yogacara Buddhist idealist school. Mind can be conceived as having two ‘parts’: the receptacle consciousness, constituted by the vasanas, or ‘marks’ left by any individual experience, which ‘remains’ in the mind in an unconscious state; and the function consciousness, constituted by these same vasanas transforming themselves into conscious ideas and representations, which are either of a cognizing ego or of congnized objects and beings and similar to the experiences that gave rise to them. Since a beginningless eternity, vasanas have been produced without anything real corresponding to them, in a fantasmagorical process.
Phthisical Insanity
Authors: Clouston T. S. , Berrios G. E.
Published: November 2005

The history of the relationship between tuberculosis and insanity has been neglected. This is surprising, for during the nineteenth century it was subject to an important medical and cultural debate and gave rise to a style of analysis which has been used ever since to study the clinical phenomenon of ‘disease-coexistence’ (rebaptized ‘comorbidity’ during the 1970s). Triggered by a perceived increase in the prevalence of tuberculosis and insanity, the debate centred around the meaning and mechanisms of disease-coexistence, techniques which may be used to rule out fortuitous associations, the comparative relevance of epidemiological, congenital, genetic and environmental factors, and the clinical effects that the members of the disease pair may have on each other. The Classic Text reprinted below provides an adequate introduction to the main issues listed above.
Free Surface Problems for Static Coulomb-Mohr Granular Solids
Authors: McCue Scott W. , Hill James M.
Published: November 2005

This paper is concerned with some plane strain and axially symmetric free surface problems which arise in the study of static granular solids that satisfy the Coulomb-Mohr yield condition. Such problems are inherently nonlinear, and hence difficult to attack analytically. Given a Coulomb friction condition holds on a solid boundary, it is shown that the angle a free surface is allowed to attach to the boundary is dependent only on the angle of wall friction, assuming the stresses are all continuous at the attachment point, and assuming also that the coefficient of cohesion is nonzero. As a model problem, the formation of stable cohesive arches in hoppers is considered. This undesirable phenomena is an obstacle to flow, and occurs when the hopper outlet is too small. Typically, engineers are concerned with predicting the critical outlet size for a given hopper and granular solid, so that for hoppers with outlets larger than this critical value, arching cannot occur. This is a topic of considerable practical interest, with most accepted engineering methods being conservative in nature. Here, the governing equations in two limiting cases (small cohesion and high angle of internal friction) are considered directly. No information on the critical outlet size is found; however solutions for the shape of the free boundary (the arch) are presented, for both plane and axially symmetric geometries.
Treloar's Biaxial Tests and Kearsley's Bifurcation in Rubber Sheets
Authors: Batra R. C. , Mueller Ingo , Strehlow Peter
Published: November 2005

We review Treloar's biaxial experiments and Kearsley's calculated instability in a square rubber sheet. Treloar's rubber is recognized as a Mooney-Rivlin material. It turns out that Treloar's test could not have anticipated Kearsley's stability analysis, since his loads were far below the critical load of bifurcation. We repeat Treloar's experiment but with much higher loads and confirm Kearsley's prediction.
Exploring Fear of General and Gang Crimes among Juveniles on Probation
Authors: Lane Jodi
Published: November 2005

This exploratory study examines fear of general and gang-related crime among juvenile probationers. Most had used alcohol and marijuana before, and many had committed at least one crime during the study period. Most were afraid of shooting and murder, and about one third were afraid of other crimes. More participation in drug use and delinquency behaviors was generally unrelated to fear.
Project Confirm
Authors: Conger Dylan , Ross Timothy
Published: November 2005

When a foster care youth has been arrested, several child-serving agencies are required to communicate effectively to ensure that a responsible guardian is present to take custody. Exploratory research suggests that, in some cases, judges detain children unnecessarily because their guardians fail to appear. This article presents the results of an evaluation of Project Confirm, a program designed to reduce the unnecessary detention of foster care youth. The evaluation reveals a disparity in pre-adjudication detention rates between foster and nonfoster juveniles with similar characteristics both before and after the introduction of the program. The lack of an average program effect on this disparity is explained by the fact that the disparity decreased for juveniles with less serious records but increased for those with more serious records. Finally, both the disparity in detention prior to the program and the program effect differed according to juveniles’ gender, race, and court county.
Loss of Response to Imatinib: Mechanisms and Management
Authors: Shah Neil P.
Published: November 2005

The treatment of chronic myeloid leukemia (CML) has been revolutionized by the small molecule BCR-ABL-selective kinase inhibitor imatinib. Although imatinib is highly effective initially and generally well-tolerated, relapse is increasingly encountered clinically. Until recently, for the majority of CML patients with disease no longer responsive to imatinib, as well as for patients with imatinib intolerance, few effective therapeutic options existed. Our understanding of the major mechanisms of imatinib resistance has led to the clinical development of two novel BCR-ABL inhibitors that harbor significant therapeutic promise in early clinical trial experience. These agents, dasatinib (BMS-354825) and AMN107, are more potent inhibitors of BCR-ABL than imatinib, and moreover, harbor activity against nearly all imatinib-resistant BCR-ABL kinase domain mutant forms tested in vitro. Notably, neither of these compounds is effective against the imatinib-resistant BCR-ABL/T315I mutation. The potential availability of highly effective medications for the treatment of imatinib-resistant and intolerant cases of CML is expected to further complicate the timing of other effective therapies, such as allogeneic stem cell transplantation. Additionally, periodic genotyping of the BCR-ABL kinase domain to screen for drug-resistant mutations may play an increasingly important role in the future management of CML cases.
Evolving Approaches to Primary Treatment of Hodgkin Lymphoma
Authors: Connors Joseph M.
Published: November 2005

Two challenges confront the clinician treating Hodgkin lymphoma today: achieving a high level of effectiveness while minimizing toxicity. At least 80% of patients can be cured with currently available chemotherapy regimens, augmented in selected patients with the addition of involved field radiation or intensified chemotherapy assisted by granulocyte growth factors or stem cell transplantation. Major late toxicity including infertility, premature menopause, cardiovascular disease and second neoplasms can be avoided in most patients if the treatment program is chosen carefully.

The extent of disease (stage) and, for advanced stage lymphoma, the presence of well-characterized prognostic factors can be established with readily available clinical, laboratory and imaging techniques. Results from carefully designed and analyzed clinical trials have identified optimal treatment approaches for patients with limited and advanced stage disease. Those with limited stage Hodgkin lymphoma should be treated with brief chemotherapy, only augmented with involved field irradiation if an early complete remission is not achieved. Most patients with advanced stage lymphoma can be cured with an extended course of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine). The small minority under the age of 60 years with an International Prognostic Factors Project score of 5 or greater should be considered for intensified chemotherapy. Patients known to have bulky tumor(s) (> 10 cm) at diagnosis may require adjuvant irradiation at the conclusion of chemotherapy, but its utility has not been unequivocally established and radiation should be avoided in those who achieve a complete remission, where it is known to be ineffective.

With careful selection of treatment program most patients found to have Hodgkin lymphoma today can be offered a high probability of cure and a low likelihood of major late toxicity. However, without detailed attention to the extent of lymphoma and other prognostic factors, there is as much danger of over-treatment as under-treatment. Only by thoughtfully adjusting the treatment program to the extent of disease and response to treatment can the clinician determine the optimal approach, maximizing likelihood of cure and minimizing late toxicity.
MGUS and Smoldering Multiple Myeloma: Update on Pathogenesis, Natural History, and Management
Authors: Rajkumar S. Vincent
Published: November 2005

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic, pre-malignant disorders characterized by monoclonal plasma cell proliferation in the bone marrow and absence of end-organ damage. Recent advances in the pathogenesis, natural history, and prognosis of MGUS and SMM are reviewed. A new risk stratification system to determine the prognosis of MGUS using the size and type of M protein, and the serum free light chain assay is discussed.
Early Genetic Events Provide the Basis for a Clinical Classification of Multiple Myeloma
Authors: Kuehl W. Michael , Bergsagel P. Leif
Published: November 2005

Multiple myeloma is a tumor of somatically mutated, isotype-switched plasma cells that accumulate in the bone marrow leading to bone destruction and bone marrow failure. The germinal center processes of somatic hypermutation and switch recombination are implicated in the development of recurrent immunoglobulin gene translocations in 40% of patients. These affect five loci: 11q13, 6p21, 4p16, 16q23 and 20q11, leading to dysregulation of CCND1, CCND2, FGFR3/MMSET, c-MAF and MAFB respectively. The remaining 60% of patients can be divided into four groups based on their expression of CCND1 and CCND2. The largest group (40%) ectopically express CCND1 bi-allelically and have hyperdiploidy with multiple trisomies of chromosomes 3, 5, 7, 9, 11, 15, 19 and 21. The translocation and cyclin D (TC) groups identify patients with different genetics, biology, clinical features, prognosis and response to therapy.
An Update of the Management of Multiple Myeloma: The Changing Landscape
Authors: Reece Donna E.
Published: November 2005

The management of multiple myeloma is rapidly changing. Cytogenetic, molecular and proteomic techniques have led to a better understanding of the pathophysiology of this heterogeneous malignancy. Novel agents designed to interrupt myeloma growth and survival pathways have entered into clinical usage with unprecedented speed, while new prognostic systems based on clinical and biologic features, such as cytogenetic abnormalities, have been developed. A plethora of clinical trials have been initiated utilizing novel agents, alone or in conjunction with established modalities such as conventional cytotoxic agents and stem cell transplantation. These newer treatments have increased the antitumor response rates in this disease and have provided options for patients whose disease has become resistant to conventional therapy. A major challenge is to define the optimal use of these new agents and combinations in order to significantly impact the natural history of myeloma.
Diagnosis and Management of Mild Bleeding Disorders
Authors: Hayward Catherine P. M.
Published: November 2005

Mild bleeding disorders are a common reason for a referral to a hematologist and these conditions can be challenging to evaluate. Recent research has highlighted that some bleeding symptoms are quite common in the general population and that there is clinical variability in symptom expression among individuals with defined bleeding problems. Moreover, bleeding risks for many bleeding disorders are unknown. This article reviews symptoms and problems that can be considered suspicious of a mild form of bleeding disorder and the diagnostic investigations useful to evaluate these problems. A stepwise approach is presented for the diagnostic evaluation, to allow detection of common and rare coagulation and fibrinolytic defects, and adequate assessments of potential von Willebrand factor and platelet problems. Some common problems in the diagnosis and management of mild bleeding problems are reviewed, including the common failure to establish a diagnosis with testing. An approach is proposed for translation of knowledge to patients who are challenged by mild bleeding problems.
Sexuality and Fertility after Cancer
Authors: Schover Leslie R.
Published: November 2005

As more people achieve long-term survival after cancer, sexual dysfunction and infertility have increasingly been recognized as negative consequences that impact quality of life. Sexual dysfunction is a frequent long-term side effect of cancer treatment, but damage to different underlying physiological systems is salient in men versus women. Men frequently have erectile dysfunction (ED) related to damage to the autonomic nervous system and/or reduced circulation of blood to the penis. Hormonal impairment of sexual function is less common. Women, in contrast, are able to overcome damage to autonomic nerves if genital tissues remain structurally intact and estrogenized. Female sexual dysfunction is frequently associated with sudden premature ovarian failure or direct effects of radiation fibrosis or scar tissue causing pain with sexual activity. The lack of validated interventions for sexual rehabilitation after cancer is a major problem, as is finding cost-effective ways of providing services. Concerns about fertility are also a major source of distress to people treated for cancer during childhood or young adulthood, yet many young survivors do not recall any discussion about future childbearing potential with their oncology team. Since fertility preservation is becoming more practical for both men and women, producing patient and professional educational materials and developing professional practice guidelines should be high priorities for oncology societies.
Familial and Acquired Hemophagocytic Lymphohistiocytosis
Authors: Janka Gritta , zur Stadt Udo
Published: November 2005

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by uncontrolled hyperinflammation on the basis of various inherited or acquired immune deficiencies. Cardinal symptoms are prolonged fever, hepatosplenomegaly and cytopenias. Central nervous system (CNS) symptoms are common. Biochemical markers include elevated triglyceride and ferritin, high levels of the α chain of the soluble interleukin-2 receptor and low fibrinogen. Impaired function of natural killer (NK) cells and cytotoxic T-cells (CTL) is a characteristic of all forms of HLH.

Genetic HLH occurs in familial forms (FHLH), in which HLH is the primary and only manifestation, and in association with the immune deficiencies Chédiak-Higashi syndrome (CHS), Griscelli syndrome (GS) and X-linked lymphoproliferative syndrome (XLP), in which secondary HLH occurs sporadically. Most patients with acquired HLH have no known underlying immune deficiency. Both acquired and genetic forms are triggered by infections, mostly viruses, or other stimuli. HLH also occurs as a complication of rheumatic diseases (macrophage activation syndrome) and of malignancies. The recent discovery of several genetic defects causing FHLH as well as the identification of the genes responsible for CHS, GS and XLP have underscored the role of granule (perforin/granzymes)-mediated cytotoxicity in both the killing of infected cells and the termination of the immune response. The immediate aim of therapy is suppression of the increased inflammatory response by immunosuppressive/immunomodulatory agents and cytotoxic drugs. Genetic cases can only be cured with stem cell transplantation. Awareness of the clinical symptoms and of diagnostic criteria for HLH is crucial to starting life-saving therapy in time.
IL-2 administration increases CD4+CD25hi Foxp3+ regulatory T cells in cancer patients
Authors: Ahmadzadeh Mojgan , Rosenberg Steven A.
Published: November 2005

Interleukin-2 (IL-2) is historically known as a T-cell growth factor. Accumulating evidence from knockout mice suggests that IL-2 is crucial for the homeostasis and function of CD4+CD25+ regulatory T cells in vivo. However, the impact of administered IL-2 in an immune intact host has not been studied in rodents or humans. Here, we studied the impact of IL-2 administration on the frequency and function of human CD4+CD25hi T cells in immune intact patients with melanoma or renal cancer. We found that the frequency of CD4+CD25hi T cells was significantly increased after IL-2 treatment, and these cells expressed phenotypic markers associated with regulatory T cells. In addition, both transcript and protein levels of Foxp3, a transcription factor exclusively expressed on regulatory T cells, were consistently increased in CD4 T cells following IL-2 treatment. Functional analysis of the increased number of CD4+CD25hi T cells revealed that this population exhibited potent suppressive activity in vitro. Collectively, our results demonstrate that administration of high-dose IL-2 increased the frequency of circulating CD4+CD25hi Foxp3+ regulatory T cells. Our findings suggest that selective inhibition of IL-2-mediated enhancement of regulatory T cells may improve the therapeutic effectiveness of IL-2 administration. (Blood. 2006;107:2409-2414)
B-lymphocyte stimulator (BLyS) stimulates immunoglobulin production and malignant B-cell growth in Waldenström macroglobulinemia
Authors: Elsawa Sherine F. , Novak Anne J. , Grote Deanna M. , Ziesmer Steven C. , Witzig Thomas E. , Kyle Robert A. , Dillon Stacey R. , Harder Brandon , Gross Jane A. , Ansell Stephen M.
Published: November 2005

Waldenström macroglobulinemia (WM) is a serious and frequently fatal B-cell malignancy associated with an elevated monoclonal IgM protein in the serum. Many of the mechanisms leading to this disease are not yet known. B-lymphocyte stimulator (BLyS) is a TNF family member that is critical for maintenance of normal B-cell development and homeostasis. BLyS is overexpressed in a variety of B-cell malignancies and has been shown to inhibit apoptosis in malignant B cells. It also regulates immunoglobulin secretion by normal B cells. To determine the relevance of BLyS in WM, we examined the role of BLyS in WM patient samples. Malignant B cells were found to bind soluble BLyS and variably express the receptors BAFF-R, TACI, and BCMA. We also found expression of BLyS in bone marrow specimens by immunohistochemistry and elevated serum BLyS levels in patients with WM. BLyS, alone or in combination with cytokines that induce immunoglobulin production, was found to increase IgM secretion by malignant B cells. Furthermore, BLyS was found to increase the viability and proliferation of malignant B cells from WM patients. Due to the role of BLyS in WM, strategies to inhibit BLyS may potentially have therapeutic efficacy in these patients.
Genome-wide identification of the regulatory targets of a transcription factor using biochemical characterization and computational genomic analysis
Authors: Jolly Emmitt R , Chin Chen-Shan , Herskowitz Ira , Li Hao
Published: November 2005

Background

A major challenge in computational genomics is the development of methodologies that allow accurate genome-wide prediction of the regulatory targets of a transcription factor. We present a method for target identification that combines experimental characterization of binding requirements with computational genomic analysis.

Results

Our method identified potential target genes of the transcription factor Ndt80, a key transcriptional regulator involved in yeast sporulation, using the combined information of binding affinity, positional distribution, and conservation of the binding sites across multiple species. We have also developed a mathematical approach to compute the false positive rate and the total number of targets in the genome based on the multiple selection criteria.

Conclusion

We have shown that combining biochemical characterization and computational genomic analysis leads to accurate identification of the genome-wide targets of a transcription factor. The method can be extended to other transcription factors and can complement other genomic approaches to transcriptional regulation.
How and why community hospital clinicians document a positive screen for intimate partner violence: a cross-sectional study
Authors: Gerber Megan R , Leiter Karen S , Hermann Richard C , Bor David H
Published: November 2005

Background

This two-part study examines primary care clinicians' chart documentation and attitudes when confronted by a positive waiting room screen for intimate partner violence (IPV).

Methods

Patients at community hospital-affiliated health centers completed a screening questionnaire in waiting rooms that primary care providers (PCPs) were subsequently given at the time of the visit. We first reviewed the medical records of patients who screened positive for IPV, evaluating the presence and quality of documentation. Next we administered a survey to PCPs that measured their knowledge, attitudes and practice regarding IPV.

Results

Seventy-two percent of charts contained some documentation of IPV, however only 10% contained both a referral and safety plan. PCPs were more likely to refer patients (p < .05) who screened positively for mood or anxiety disorders, disclosed that they feared for their safety or were economically disadvantaged. Those that feared for their safety or endorsed mood or anxiety disorders were more likely to have notation of a safety plan in their records. When surveyed, 81.6% of clinicians strongly agreed that it is their role to inquire about IPV, but only 68% expressed confidence in their ability to manage it. In contrast, 93% expressed confidence in managing depression. Sixty-seven percent identified time constraints as a barrier to care. Predictors of PCP confidence in treating patients who have experienced IPV (p < .05) included hours of recent training and clinical experience with IPV.

Conclusion

Mandatory waiting room screening for IPV does not result in high levels of referral or safety planning by PCPs. Despite the implementation of a screening process, clinicians lack confidence and time to address IPV in their patient populations suggesting that alternative methods of training and supporting PCPs need to be developed.
Smoking, oxidative stress and inflammation: Impact on resting energy expenditure in diabetic nephropathy
Authors: Agarwal Rajiv
Published: November 2005

Background

Inflammation is associated with increased resting energy expenditure (REE) in patients with chronic kidney disease. Oxidative stress, on the other hand, appears not to increase REE. Smoking is a common mechanism for generating oxidative stress and inflammation. Whether smokers have increased REE and if so, whether it is accounted for by the pro-oxidant and inflammatory state is not known.

Methods

A case control study of 11 smokers and 24 non-smokers with overt diabetic nephropathy was performed to evaluate the chronic effect of smoking on REE. REE (indirect calorimetry), glomerular filtration rate (iothalamate clearance), markers of oxidative stress (urinary and plasma malondialdehyde (MDA), and protein carbonyls) and inflammation (C-reactive protein, tumor necrosis factor-alpha, interleukin-6) were measured on two occasions four months apart.

Results

Biomarkers of inflammation (C-reactive protein) and oxidative stress (urinary and plasma MDA) were increased in smokers. REE was increased in smokers, 24.3 kcal/kg/day compared to 21 kcal/kg/day (p = 0.009) in non-smokers. After adjusting for age, GFR, MDA, C-reactive protein, and hemoglobin A1C the difference in REE between the two groups persisted (adjusted difference 3.51 kcal/kg/d, 95% confidence interval 0.59 – 6.45, p = 0.020).

Conclusion

Patients with overt diabetic nephropathy who smoke have a higher REE, oxidative and inflammatory state. Elevated REE is not attributable to heightened oxidative stress and inflammatory state. Smoking is an independent risk factor for elevated REE in patients with diabetic nephropathy and provides an additional mechanism by which it may lead to poor outcomes.
Teratoma occupying the left hemithorax
Authors: Zisis Charalambos , Rontogianni Dimitra , Stratakos Grigorios , Voutetakis Konstantinos , Skevis Konstantinos , Argiriou Mihalis , Bellenis Ion
Published: November 2005

Background

Teratomas are manifested with a great variety of clinical and radiological features, while sometimes they simply represent incidental findings.

Case presentation

A rare case of benign teratoma of the dermoid cyst type, in an adult 40-year-old female patient, is reported. The patient had presented recurrent pulmonary infections for the previous 2 months, persistent cough, and progressively aggravating dyspnea. A chest X-ray showed total atelectasis of the left lung, and the thoracic CT-scan revealed a huge mass, containing multiple elements of heterogeneous density, probably originating from the mediastinum, occupying the whole left hemithorax. The mass compressed the vital structures of the mediastinum, great vessels and airways, and a chest MRI was performed to accurately detect the anatomical relations. The patient underwent left thoracotomy and the tumor was totally resected. The size of the tumor was extremely large although no invasion to the vessels or to the airway had occurred. Adherence to the adjacent left pulmonary artery and left main bronchus was present, but without erosion or fistulization. The postoperative course was uneventful, while the histological examination confirmed a teratoma.

Conclusion

A teratoma is a non-homogeneous pathological entity, clinically, radiologically or histologically. It is predominantly diagnosed between the second and fourth decade and the incidence is equal for both sexes. Symptoms are absent in one half of the patients. The case reported is noteworthy as the tumor appeared with total atelectasis of the left lung, and symptoms started 2 months prior to diagnosis. Total removal of the tumor is adequate treatment for this type of teratoma and the prognosis is excellent.