bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the Mechanical Properties of ENR/NBR Blends via Masterbatches with Initial Accelerator Concentration Gradients
Authors: Sahakaro K. , Pantupon N.
Published: April 2008

Epoxidized natural rubber with 30 mol.% of epoxide (ENR-30) was blended with medium nitrile rubber (NBR) at the blend weight ratios of 30/70 and 70/30. Blend compounds were prepared via simple mixing and masterbatch techniques using TBBS as an accelerator. The masterbatches of ENR-30 initially consisted of higher accelerator concentrations compared with those of NBR, in order to compensate an effect of accelerator partition towards NBR phase. The initial accelerator concentration ratios in ENR-30 and NBR masterbatches before blending were at 50/50, 60/40, 70/30 and 80/20, respectively. The blend vulcanizates prepared by masterbatch mixing showed a significant improvement in tensile properties in comparison with those prepared by simple blend, and the initial accelerator concentration ratio in ENR-30/NBR masterbatches at 70/30 gave the highest ultimate tensile properties. The improvement in tensile properties was clearly observed for all the blends vulcanized with conventional, semi-EV and EV sulfur-vulcanization systems. The increase of tensile properties does suggest a better curative distribution, and hence a better crosslink distribution.
Effects of Hot-drawing and Annealing on the Morphology and Mechanical Properties of Biodegradable Polyester Monofilament Fibers
Authors: Siripitayananon J. , Molloy R. , Bunkird S. , Kleawkla A. , Panjakha R. , Chooprayoon P.
Published: April 2008

Co/terpolymers of L-lactide (LL), ∊-caprolactone (CL) and glycolide (G) are biodegradable in the human body and, as such, have considerable potential for use in biomedical applications such as absorbable surgical sutures, nerve guides, bone fixation devices and drug delivery systems. This study focuses its attention on their potential as monofilament fibers for absorbable suture applications. Random co/terpolymers with different compositions of LL, CL and G were synthesized via bulk ring-opening polymerization. The polymers obtained were melt spun at slow speeds into ice-cooled water to produce as-spun monofilament fibers with as little molecular orientation and crystallinity as possible. Combinations of off-line hot-drawing and annealing steps under controlled conditions of draw rate, draw ratio, temperature and time were then employed in order to develop the fiber's oriented semi-crystalline morphology. The mechanical properties of the fibers were tested after each processing step and compared. The tensile test results showed that the tensile strength was strongly dependent on the draw ratio. A high draw ratio was obtained by multiple off-line hot-drawings with intermediate annealing. The first hot-drawing step dramatically enhanced the mechanical properties relative to those of the weak, highly extensible as-spun fiber. Subsequent annealing at a suitable temperature and for an appropriate length of time increased fiber flexibility as a result of molecular relaxation. Additional hot-drawing steps, again under precise temperature-time conditions, increased the total draw ratio and further enhanced the fiber's mechanical strength.
The Effect of CO2 Pressure on Viscoelasticity of LDPE
Authors: Ouchi S. , Masubuchi Y. , Shikuma H.
Published: April 2008

The effect of impregnated carbon dioxide (CO2) and pressure on dynamic viscoelastic responce of a commercial LDPE was investigated by a magnetic driven rotational rheometer equipped with a high-pressure chamber. It was found that i) the mode distribution of the viscoelastic relaxation is not sensitive to CO2 pressure realizing the superposition among moduli obtained at different pressures, that ii) the horizontal shift factor for the superposition reflecting the monomeric friction exponentially decreases with increase of the pressure, and that iii) the vertical shift factor relating to the entanglement number density is not sensitive to the pressure. From the observation it is suggested that CO2 and pressure mainly affect the monomeric friction and the effect on the entanglement dilation is not significant. The results are consistent with the dielectric measurement on polyisoprene (Matsumiya et al., Nihon Reoroji Gakkaishi, 35, 155–161, 2007).
Interfacial Characteristics of Film Insert Moldings Consisting of Semicrystalline and Amorphous Polymers
Authors: Leong Y. W. , Hamada H.
Published: April 2008

Film insert moldings were produced from amorphous and crystalline polymers, i. e. PC + ABS and PET respectively. The vastly different characteristics of these polymers provide an interesting platform to study the mechanisms that are responsible for interfacial bond formation, particularly when these materials were molded at different molding conditions. It was observed that intermolecular diffusion between amorphous polymers takes place at virtually any temperature as long as it is kept above the glass transition temperature of the material, though higher temperatures are favorable to accelerate diffusion. As for crystalline polymers, there is an initial need to create free and mobile molecular chains by heating the materials to its melting temperature before any significant diffusion takes place. Certain criteria have to be met, irrespective of the materials used, before good interfacial bonding is achieved. Firstly, the injection molding parameters should be optimized to ensure intimacy between the surfaces of the film and injected resin. Once this is achieved, interdiffusion of molecules should be promoted to ensure extensive film-substrate molecular entanglements. The state of molecular entanglement should then be retained for a sufficient amount of time as the material solidifies in order to obtain good film-substrate adhesion.
Israel's Future: The Time Factor
Authors: Inbar Efraim , Lustick Ian S.
Published: April 2008

A Debate between Efraim Inbar and Ian S. Lustick

Time is on Israel's Side
Efraim Inbar

From a realpolitik perspective, the balance of power between Israel and its neighbors is the critical variable in the quest for survival in a bad neighborhood. If Israel’s position is improving over time and the power differential between the Jewish State and its foes is growing, then its capacity to overcome regional security challenges is assured. Moreover, under such circumstances there is less need to make concessions to weaker parties that are in no position to exact a high price from Israel for holding on to important security and national assets such as the Golan Heights, the settlement blocs close to the “Green Line,” the Jordan Rift, and particularly Jerusalem.

With a Bang or a Whimper, Time Is Running Out
Ian S. Lustick

Israel’s existence in the Middle East is fundamentally precarious. Twentieth-
century Zionism and Israeli statehood is but a brief moment in Jewish history. There is nothing more regular in Jewish history and myth than Jews “returning” to the Land of Israel to build a collective life—nothing more regular, that is, except, for Jews leaving the country and abandoning the project. Abraham came from Mesopotamia, then left for Egypt. Jacob left for Hauran, then returned, then left with his sons for Egypt. The Israelites
subsequently left Egypt with Moses and Joshua, and “returned” to the Land. Upper class Jews who did not leave with the Assyrians left with Jeremiah for Babylon, then returned with Ezra and Nehemiah.
Zionism between Raw Force and Eros: Berdichevski's Passionate Relation to the Jewish Political Revolution
Authors: Amiran-Sappir Revital
Published: April 2008

This article deals with the relation of Micha Yosef Ben Gurion (Berdichevski)—one of the central formulators of the Zionist idea and of modern Hebrew literature—to the Zionist political sphere. As a wordly Jewish intellectual, Berdichevski attempted to establish a kind of Zionism that would allow Jewish individuals to engage in it as an act of their desires. In exploring how his carnal inclinations affected his vision of the political, I argue that Berdichevski's perception fails qualitatively by transposing its guiding sensual approach to the formulation of the new Jewish political sphere. As this article will show, Berdichevski's relation to the Jewish political revolution reveals a sometimes limited perception regarding the possibilities of freedom inherent in political activity and often contradicts his own aspiration to nurture the liberty of Jewish individuals.
Making Peace with the Duel of Narratives: Dual-Narrative Texts for Teaching the Israeli-Palestinian Conflict
Authors: Lazarus Ned
Published: April 2008

Sami Adwan and Dan Bar-On, eds., Learning the Other’s Historical Narrative: Israelis and Palestinians, Parts One and Two (Beit Jalla: Peace Research Institute in the Middle East, 2003, 2006).

Robert I. Rotberg, ed., Israeli and Palestinian Narratives of Conflict: History’s Double Helix (Bloomington: Indiana University Press, 2006).

Paul Scham, Walid Salem, and Benjamin Pogrund, eds., Shared Histories: A Palestinian-Israeli Dialogue (Walnut Creek, CA: Left Coast Press, 2005).
Cosmopolitanism and the French Anti-GM Movement
Authors: Williams Gwyn
Published: April 2008

This paper explores the rights-based cosmopolitanism of French anti-GM activists and their challenge to the neoliberal cosmopolitanism of the World Trade Organization and multinational corporations. Activists argue that genetic modification, patents, and WTO-brokered free trade agreements are the means by which multinationals deny people fundamental rights and seek to dominate global agriculture. Through forms of protest, which include cutting down field trials of genetically modified crops, activists resist this agenda of domination and champion the rights of farmers and nations to opt out of the global agricultural model promoted by biotechnology companies. In so doing, they defend the local. This defense, however, is based on a cosmopolitan discourse of fundamental rights and the common good. I argue that activists' cosmopolitan perspective does not transcend the local but is intimately related to a particular understanding of it.
Radiation-induced meningioma
Authors: Umansky Felix , Shoshan Yigal , Rosenthal Guy , Fraifeld Shifra , Spektor Sergey
Published: April 2008

✓ The long-term or delayed side effects of irradiation on neural tissue are now known to include the induction of new central nervous system neoplasms. However, during the first half of the 20th century, human neural tissue was generally considered relatively resistant to the carcinogenic and other ill effects of ionizing radiation. As a result, exposure to relatively high doses of x-rays from diagnostic examinations and therapeutic treatment was common.

In the present article the authors review the literature relating to radiation-induced meningiomas (RIMs). Emphasis is placed on meningiomas resulting from childhood treatment for primary brain tumor or tinea capitis, exposure to dental x-rays, and exposure to atomic explosions in Hiroshima and Nagasaki. The incidence and natural history of RIMs following exposure to high- and low-dose radiation is presented, including latency, multiplicity, histopathological features, and recurrence rates. The authors review the typical presentation of patients with RIMs and discuss unique aspects of the surgical management of these tumors compared with sporadic meningioma, based on their clinical experience in treating these lesions.
Pituitary apoplexy: correlation between magnetic resonance imaging and histopathological results
Authors: Semple Patrick L. , Jane John A. , Lopes M. Beatriz S. , Laws Edward R.
Published: April 2008

Object

The aim of this study was to correlate the magnetic resonance (MR) imaging findings in pituitary apoplexy with histopathological results and determine whether the histopathology influences clinical presentation and outcome.

Methods

The records of 36 patients with histologically confirmed pituitary apoplexy, who were treated surgically at the University of Virginia Health System between 1996 and 2006, were retrospectively reviewed. The MR images were divided into 3 groups: 1) infarction alone; 2) hemorrhage with or without infarction; and 3) tumor only with no evidence of apoplexy. The histological examination was divided into infarction alone or hemorrhagic infarction/hemorrhage. The MR imaging findings were then correlated with the histopathological results to assess how accurately the histopathology was predicted by the MR imaging. The clinical features and outcomes of the two histopathological groups were also compared.

Results

The MR imaging findings were able to predict the histopathology accurately in the majority of cases. The group of patients with infarction had less severe clinical features and a better outcome than those with hemorrhagic infarction/hemorrhage.

Conclusions

Magnetic resonance imaging findings in the setting of pituitary apoplexy accurately predict the nature of the apoplectic process and help to guide the type and timing of therapy.
Successful inhibition of intracranial human glioblastoma multiforme xenograft growth via systemic adenoviral delivery of soluble endostatin and soluble vascular endothelial growth factor receptor-2
Authors: Szentirmai Oszkar , Baker Cheryl H. , Bullain Szofia S. , Lin Ning , Takahashi Masaya , Folkman Judah , Mulligan Richard C. , Carter Bob S.
Published: April 2008

Object

Glioblastoma multiforme (GBM) is characterized by neovascularization, raising the question of whether angiogenic blockade may be a useful therapeutic strategy for this disease. It has been suggested, however, that, to be useful, angiogenic blockade must be persistent and at levels sufficient to overcome proangiogenic signals from tumor cells. In this report, the authors tested the hypothesis that sustained high concentrations of 2 different antiangiogenic proteins, delivered using a systemic gene therapy strategy, could inhibit the growth of established intracranial U87 human GBM xenografts in nude mice.

Methods

Mice harboring established U87 intracranial tumors received intravenous injections of adenoviral vectors encoding either the extracellular domain of vascular endothelial growth factor receptor-2-Fc fusion protein (Ad-VEGFR2-Fc) alone, soluble endostatin (Ad-ES) alone, a combination of Ad-VEGFR2-Fc and Ad-ES, or immunoglobulin 1-Fc (Ad-Fc) as a control.

Results

Three weeks after treatment, magnetic resonance imaging-based determination of tumor volume showed that treatment with Ad-VEGFR2-Fc, Ad-ES, or Ad-VEGFR2-Fc in combination with Ad-ES, produced 69, 59, and 74% growth inhibition, respectively. Bioluminescent monitoring of tumor growth revealed growth inhibition in the same treatment groups to be 62, 74, and 72%, respectively. Staining with proliferating cell nuclear antigen and with terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling showed reduced tumor cell proliferation and increased apoptosis in all antiangiogenic treatment groups.

Conclusions

These results suggest that systemic delivery and sustained production of endostatin and soluble VEGFR2 can slow intracranial glial tumor growth by both reducing cell proliferation and increasing tumor apoptosis. This work adds further support to the concept of using antiangiogenesis therapy for intracranial GBM.
Neurosurgical implications of mannitol accumulation within a meningioma and its peritumoral region demonstrated by magnetic resonance spectroscopy
Authors: Sankar Tejas , Assina Rachid , Karis John P. , Theodore Nicholas , Preul Mark C.
Published: April 2008

✓Mannitol is widely considered the hyperosmolar therapy of choice in routine neurosurgical practice for the reduction of intracranial pressure (ICP). The authors present a unique case of a patient with a large meningioma treated with mannitol, in which mannitol accumulation within the tumor and its surrounding parenchyma was shown using in vivo magnetic resonance spectroscopy (MRS). This rare appearance of mannitol on MRS was characterized by a wide-based peak at 3.8 ppm, which remained detectable several hours after the last dose. These findings provide the first in vivo evidence in support of the prevailing theory that mannitol leakage into the peritumoral edematous region may contribute to rebound increases in ICP and suggest that this phenomenon has the potential to occur in extraaxial tumors. Judicious use of mannitol in the setting of elevated ICP due to tumor may be indicated to avoid potentially deleterious side effects caused by its accumulation.
Metastatic choriocarcinoma with multiple neoplastic intracranial microaneurysms
Authors: Chang In Bok , Cho Byung Moon , Park Se Hyuck , Yoon Dae Young , Oh Sae Moon
Published: April 2008

✓The authors report on a case of a metastatic choriocarcinoma that mimicked systemic necrotizing vasculitis on a cerebral angiogram. A 35-year-old woman presented with right hemiplegia and a drowsy mental state. A computed tomography (CT) scan revealed an intracerebral hemorrhage in the left frontal region. A cerebral angiogram showed multiple microaneurysms arising from the bilateral anterior cerebral arteries and middle cerebral arteries, and the renal angiogram showed multiple microaneurysms arising from the left distal renal artery. A chest CT scan revealed multiple metastatic lesions in the left lower lung field. The hematoma and microaneurysms were surgically removed. Choriocarcinoma was diagnosed after histological examination. Despite receiving postoperative chemotherapy, the patient died 1 month after the operation.
Non-Hodgkin lymphoma of the cranial vault with retrobulbar metastasis mimicking a subacute subdural hematoma
Authors: Yoon Sang-Hoon , Paek Sun Ha , Park Sung-Hye , Kim Dong Gyu , Jung Hee-Won
Published: April 2008

✓Primary skeletal non-Hodgkin lymphoma is rare. The authors report a case of a small lymphocytic B-cell lymphoma of the skull occurring in a 53-year-old man who presented with right-hand apraxia. Initial computed tomography and magnetic resonance imaging revealed a hematoma-mimicking lesion in the left frontoparietal subdural area. A frontotemporoparietal craniectomy and biopsy procedure yielded a diagnosis of small lymphocytic B-cell lymphoma, with a metastatic nodule in the retrobulbar area. Three years after undergoing radiation therapy and surgery, the patient has shown neurological improvement without systemic dissemination of the malignancy. The lesion in this case was misdiagnosed as a subdural hematoma, and shows the importance of including lymphoma in the differential diagnosis of subdural mass lesions.
Intraorbital and intracranial soft-tissue glomus tumor in an 8-year-old child
Authors: Hankinson Todd C. , Ogden Alfred T. , Canoll Peter , Garvin James H. , Kazim Michael , Bruce Jeffrey N. , Feldstein Neil A. , Anderson Richard C. E.
Published: April 2008

✓ Soft-tissue glomus tumors (or glomangiomas) are unrelated to neuroendocrine paragangliomas (glomus tympanicum, jugulare, and vagale). The authors present the first reported case of an orbital soft-tissue glomus tumor in a child. An 8-year-old girl developed rapidly progressive right-eye blindness, proptosis, and a sixth cranial nerve palsy. Magnetic resonance imaging demonstrated a homogeneously enhancing lesion extending from the right orbit through the superior orbital fissure to the cavernous sinus and middle cranial fossa. A biopsy specimen demonstrated the lesion to be a soft-tissue glomus tumor. Following angiography and embolization, a gross-total resection of the tumor was achieved. The patient was treated with adjuvant proton-beam radiotherapy. At 24 months follow-up her proptosis and sixth cranial nerve palsy had resolved and there was no evidence of tumor recurrence.
Traumatic dissecting aneurysm at the vertebrobasilar junction in a 3-month-old infant: evaluation and treatment strategies
Authors: Wang Huan , Orbach Darren B.
Published: April 2008

✓Intracranial aneurysms in young infants are extremely rare, with few published reports on the etiology, evaluation, treatment strategies, and follow-up of this condition in this population. The authors report the case of a traumatic dissecting aneurysm at the vertebrobasilar junction (VBJ) in a 3-month-old infant caused by nonaccidental trauma. Therapeutic occlusion of the VBJ was contemplated, but coil embolization of the main aneurysm sac proved feasible, and anticoagulation and antiplatelet agents were initiated. The patient made a full neurological recovery, and follow-up studies demonstrated stable aneurysm occlusion. Management and follow-up strategies for this challenging condition are discussed.
The biomechanical effectiveness of prophylactic vertebroplasty: a dynamic cadaveric study
Authors: Oakland Robert J. , Furtado Navin R. , Wilcox Ruth K. , Timothy Jake , Hall Richard M.
Published: April 2008

Object

The purpose of the study was to investigate the segmental effects of prophylactic vertebroplasty under increasingly demanding loading conditions and to assess the effect of altered cement properties on the construct biomechanics.

Methods

Twelve human cadaveric 3-vertebral functional spinal units (T12–L2) were prepared such that the intact L-1 vertebra was prophylactically augmented with cements of differing elastic moduli (100, 50, 25, and 12.5% modulus of the base cement). These specimens were subjected to quasistatic subfailure compression pre- and postaugmentation to 50% of the predicted failure strength and then cyclic loading in a fatigue rig (115,000 cycles) to characterize the high-stress, short-cycle fatigue properties of the construct. Loading was increased incrementally in proportion to body weight to a maximum of 3.5 × body weight. Quantitative computed tomography assessment was conducted pre- and postaugmentation and following cyclic testing to assess vertebral condition, cement placement, and fracture classification.

Results

Adjacent and periaugmentation fractures were induced in the prophylactically augmented segments. However, it appeared that these fractures mainly occurred when the specimens were subjected to loads beyond those that may commonly occur during most normal physiological activities.

Conclusions

Lowering the elastic modulus of the cement appeared to have no significant effect on the frequency or severity of the induced fracture within the vertebral segment.
Community-Acquired Methicillin-Resistant Staphylococcus aureus (CA-MRSA) Colonization and Infection in Intravenous and Inhalational Opiate Drug Abusers
Authors: El-Sharif Amany , Ashour Hossam M.
Published: April 2008

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen in hospital-acquired and community-acquired infections. We hypothesized that drug abuse is a risk factor for community-acquired MRSA (CA-MRSA) infection, and we employed a rapid multiplex PCR technique for MRSA identification. The study was conducted on MRSA isolates from 60 opiate addicts (intravenous and inhalational drug users) to detect the rate and location of MRSA colonization and infection among them in comparison to 60 non-addict patients and 15 healthy volunteer controls. The proportion of addicts with MRSA colonization (and/or infection) was significantly higher than non-addict patients with MRSA colonization. MRSA colonization was associated with infection in 58% of MRSA-colonized addicts. The MRSA nasal carriage in the addicts was significantly higher than MRSA carriage elsewhere, whether in the addicts group or in the non-addict patients group. Moreover, the nasopharyngeal carriage rate of MRSA among addicts was significantly higher than among the non-addict patients. Increasing the duration of addiction resulted in a significant increase in CA-MRSA colonization in opiate addicts. Both inhalational and intravenous drug use led to significant MRSA colonization in the addict population. In conclusion, this study demonstrated how drug abusers, a high-risk group for infections with MRSA, could be a source or a reservoir of CA-MRSA infection in the non-addict population.
Overexpression of Transferrin Receptor and Ferritin Related to Clinical Symptoms and Destabilization of Human Carotid Plaques
Authors: Li Wei , Xu Li-Hua , Forssell Claes , Sullivan Jerome L. , Yuan Xi-Ming
Published: April 2008

Accumulation of tissue iron has been implicated in development of atherosclerotic lesions mainly because of increased iron-catalyzed oxidative injury. However, it remains unknown whether cellular iron import and storage in human atheroma are related to human atheroma development. We found that transferrin receptor 1 (TfR1), a major iron importer, is highly expressed in foamy macrophages and some smooth muscle cells in intimal lesions of human carotid atheroma, mainly in cytoplasmic accumulation patterns. In 52 human carotid atherosclerotic lesions, TfR1 expression was positively correlated with macrophage infiltration, ectopic lysosomal cathepsin L, and ferritin expression. Highly expressed TfR1 and ferritin in CD68-positive macrophages were significantly associated with development and severity of human carotid plaques, smoking, and patient’s symptoms. The findings suggest that pathologic macrophage iron metabolism may contribute to vulnerability of human atheroma, established risk factors, and their clinical symptoms. The cytoplasmic overexpression of TfR1 may be the result of lysosomal dysfunction and ectopic accumulation of lysosomal cathepsin L caused by atheroma-relevant lipids in atherogenesis.
REDUCED ORDER GALERKIN MODELS OF FLOW AROUND NACA‐0012 AIRFOIL
Authors: Stankiewicz W. , Morzyński M. , Noack B.R. , Tadmor G.
Published: April 2008

The construction of low‐dimensional models of the flow, containing only reduced number of degrees of freedom, is the essential prerequisite of closed‐loop control of that flow. Presently used models usually base on the Galerkin method, where the flow is approximated by the number of modes and coefficients. The velocities are computed from a system of ordinary differential equations, called Galerkin System, instead of Navier‐Stokes equation. In this paper, reduced order models of the flow around NACA‐0012 airfoil are presented. The chosen mode sets include POD modes from Karhunen‐Loeve decomposition (which require previous direct numerical simulation), as well as different eigenmodes from global stability analysis of the flow.
NUMERICAL METHOD FOR 2D SOLITON SOLUTION AT SHG IN MEDIA WITH TIME‐DEPENDENT COMBINED NONLINEARITY
Authors: Trofimov V. A. , Matusevich O. V.
Published: April 2008

The paper describes the iteration method for finding the eigenfunctions and eigenvalues of the system of two nonlinear Schrödinger equations, which describes the process of second harmonic generation by femtosecond pulse in media with the quadratic and cubic nonlinear response. Coefficients, which characterize the nonlinearities, depend on one of the coordinate. The discussed method allows to find soliton solutions of new form corresponding to the first and second eigenvalues for the wide range of the nonlinear coefficients values. For determination of the eigenfunctions of the third and higher order it is necessary to select the initial approximation in a special way.
BRANCH AND BOUND WITH SIMPLICIAL PARTITIONS FOR GLOBAL OPTIMIZATION
Authors: Žilinskas J.
Published: April 2008

Branch and bound methods for global optimization are considered in this paper. Advantages and disadvantages of simplicial partitions for branch and bound are shown. A new general combinatorial approach for vertex triangulation of hyper‐rectangular feasible regions is presented. Simplicial partitions may be used to vertex triangulate feasible regions of non rectangular shape defined by linear inequality constraints. Linear inequality constraints may be used to avoid symmetries in optimization problems.
ON THE ASYMPTOTIC BEHAVIOR OF A DISCRETE TIME INSPECTION GAME
Authors: Krieger T.
Published: April 2008

In many material processing and storing plants an inspector performs during some reference time interval, e.g. one year, a number of inspections because it can not be excluded that the plant operator acts illegally by violating agreed rules, e.g., diverts valuable material. The inspections guarantee that any illegal action is detected at the earliest inspection following the beginning of that illegal action. We assume that the inspector wants to choose the time points for his inspections such that the time which elapses between the beginning of the illegal action and its detection is minimized whereas the operator wants to start his illegal action such that the elapsed time is maximized. Therefore, this inspection problem is modelled as a zero‐sum game with strategies and payoffs as described. Depending on the concrete situation the start of the illegal action and the inspections can take place either at a finite number of time points or at every time point of a reference period. The first case can be modelled as a zero‐sum game with finite pure strategy sets while the latter one leads to a zero‐sum game with infinite pure strategy sets and discontinuous payoff kernel.
ASYMPTOTIC METHOD FOR APPROXIMATION OF RESONANT INTERACTION OF NONLINEAR MULTIDIMENSIONAL HYPERBOLIC WAVES
Authors: Krylovas A.
Published: April 2008

A method of averaging along characteristics of weakly nonlinear hyperbolic systems, which was presented in earlier works of the author for one dimensional waves, is generalized for some cases of multidimensional wave problems. In this work we consider such systems and discuss a way to use the internal averaging along characteristics for new problems of asymptotical integration.
INVERTIBILITY PROPERTIES OF MATRIX WIENER‐HOPF PLUS HANKEL INTEGRAL OPERATORS
Authors: Bogveradze G. , Castro L. P.
Published: April 2008

We consider matrix Wiener‐Hopf plus Hankel operators acting between Lebesgue spaces on the real line with Fourier symbols presenting some even properties (which in particular include unitary matrix‐valued functions), and also with Fourier symbols which contain sectorial matrices. In both situations, different conditions are founded to ensure the operators invertibility, one‐sided invertibility, Fredholm property, and the so‐called nand d‐normal properties. An example is provided to illustrate the proposed theory.
RELAXATION OF A WEAKLY DISCONTINUOUS FUNCTIONAL DEPENDING ON ONE CONTROL FUNCTION
Authors: Raitums U.
Published: April 2008

The paper considers an optimal control problem of the typewhere the set M of admissible controls consists of all measurable vector‐functions h, which can take only two values h1 or h2. It is shown that the relaxation of this problem can be explicitly computed by rank‐one laminates.
Systemic Lupus Erythematosus
Authors: Siegel Caroline H. , Sammaritano Lisa R.
Published: April 2024

Importance

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation and immune-mediated injury to multiple organ systems, including the mucocutaneous, musculoskeletal, hematologic, and kidney systems. Approximately 3.4 million people worldwide have received a diagnosis of SLE.

Observations

Approximately 90% of people with SLE are female. Although there are no uniformly accepted diagnostic criteria for SLE, the 2019 European Alliance of Associations for Rheumatology (formerly the European League Against Rheumatism)/American College of Rheumatology classification criteria developed for scientific study are an estimated 96.1% sensitive and 93.4% specific for SLE. These classification criteria include both clinical factors, such as fever, cytopenia, rash, arthritis, and proteinuria, which may be indicative of lupus nephritis; and immunologic measures, such as SLE-specific autoantibodies and low complement levels. Approximately 40% of people with SLE develop lupus nephritis, and an estimated 10% of people with lupus nephritis develop end-stage kidney disease after 10 years. The primary goal of treatment is to achieve disease remission or quiescence, defined by minimal symptoms, low levels of autoimmune inflammatory markers, and minimal systemic glucocorticoid requirement while the patient is treated with maintenance doses of immunomodulatory or immunosuppressive medications. Treatment goals include reducing disease exacerbations, hospitalizations, and organ damage due to the disease or treatment toxicity. Hydroxychloroquine is standard of care for SLE and has been associated with a significant reduction in mortality. Treatments in addition to hydroxychloroquine are individualized, with immunosuppressive agents, such as azathioprine, mycophenolate mofetil, and cyclophosphamide, typically used for treating moderate to severe disease. Three SLE medications were recently approved by the Food and Drug Administration: belimumab (for active SLE in 2011 and for lupus nephritis in 2020), voclosporin (for lupus nephritis), and anifrolumab (for active SLE).

Conclusions and Relevance

Systemic lupus erythematosus is associated with immune-mediated damage to multiple organs and increased mortality. Hydroxychloroquine is first-line therapy and reduces disease activity, morbidity, and mortality. When needed, additional immunosuppressive and biologic therapies include azathioprine, mycophenolate mofetil, cyclophosphamide, belimumab, voclosporin, and anifrolumab.
Single Ascending and Multiple-Dose Trial of Zerlasiran, a Short Interfering RNA Targeting Lipoprotein(a)
Authors: Nissen Steven E. , Wolski Kathy , Watts Gerald F. , Koren Michael J. , Fok Henry , Nicholls Stephen J. , Rider David A. , Cho Leslie , Romano Steven , Melgaard Carrie , Rambaran Curtis
Published: April 2024

Importance

Lipoprotein(a) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic stenosis, with no pharmacological treatments approved by regulatory authorities.

Objectives

To assess the safety and tolerability of zerlasiran, a short interfering RNA targeting hepatic synthesis of apolipoprotein(a), and effects on serum concentrations of lipoprotein(a).

Design, Setting, and Participants

Single- and multiple-dose study in healthy participants and patients with stable ASCVD, respectively, with lipoprotein(a) serum concentrations greater than 150 nmol/L, conducted at 7 research sites in the US, the Netherlands, UK, and Australia between November 18, 2020, and February 8, 2023, with last follow-up on August 23, 2023.

Interventions

Participants were randomized to receive (1) a single subcutaneous dose of placebo (n = 8), zerlasiran 300 mg (n = 6) or 600 mg (n = 6); or (2) 2 doses of placebo (n = 9), zerlasiran 200 mg (n = 9) at a 4-week interval or 300 mg (n = 9) or 450 mg (n = 9) at an 8-week interval.

Main Outcomes Measures

The primary outcome was safety and tolerability. Secondary outcomes included serum levels of zerlasiran and effects on lipoprotein(a) serum concentrations.

Results

Among 37 patients in the multiple-dose group (mean age, 56 [SD, 10.4] years; 15 [42%] women), 36 completed the trial. Among 14 participants with extended follow-up after single doses, 13 completed the trial. There were no serious adverse events. Median baseline lipoprotein(a) concentrations in the multiple-dose group were 288 (IQR, 199-352) nmol/L. Median changes in lipoprotein(a) concentration at 365 days after single doses were 14% (IQR, 13% to 15%) for the placebo group, −30% (IQR, −51% to −18%) for the 300 mg of zerlasiran group, and −29% (IQR, −39% to −7%) for the 600-mg dose group. After 2 doses, maximal median changes in lipoprotein(a) concentration were 19 (IQR, −17 to 28) nmol/L for the placebo group, −258 (IQR, −289 to −188) nmol/L for the 200 mg of zerlasiran group, −310 (IQR, −368 to −274) nmol/L for the 300-mg dose group, and −242 (IQR, −343 to −182) nmol/L for the 450-mg dose group, with maximal median percent change of 7% (IQR, −4% to 21%), −97% (IQR, −98% to −95%), −98% (IQR, −99% to −97%), and −99% (IQR, −99% to −98%), respectively, attenuating to 0.3% (IQR, −2% to 21%), −60% (IQR, −71% to −40%), −90% (IQR, −91% to −74%), and −89% (IQR, −91% to −76%) 201 days after administration.

Conclusions

Zerlasiran was well tolerated and reduced lipoprotein(a) concentrations with infrequent administration.

Trial Registration

ClinicalTrials.gov Identifier: NCT04606602
I Read Health Information Online—Can I Trust It?
Authors: Johnson-Arbor Kelly
Published: April 2024

This JAMA Internal Medicine Patient Page describes what health misinformation is and how to find more reliable health information online.
Trajectories of Health Care Contact Days for Patients With Stage IV Non–Small Cell Lung Cancer
Authors: Gupta Arjun , Nguyen Paul , Kain Danielle , Robinson Andrew G. , Kulkarni Amit A. , Johnson David H. , Presley Carolyn J. , Blaes Anne H. , Rocque Gabrielle B. , Ganguli Ishani , Booth Christopher M. , Hanna Timothy P.
Published: April 2024

Importance

Patients with stage IV non–small cell lung cancer (NSCLC) experience substantial morbidity and mortality. Contact days (ie, the number of days with health care contact outside the home) measure how much of a person’s life is consumed by health care, yet little is known about patterns of contact days for patients with NSCLC.

Objective

To describe the trajectories of contact days in patients with stage IV NSCLC and how trajectories vary by receipt of cancer-directed treatment in routine practice.

Design, Setting, and Participants

A retrospective, population-based decedent cohort study was conducted in Ontario, Canada. Participants included adults aged 20 years or older who were diagnosed with stage IV NSCLC (January 1, 2014, to December 31, 2017) and died (January 1, 2014, to December 31, 2019); there was a maximum 2-year follow-up. Data analysis was conducted from February 22 to August 16, 2023.

Exposure

Systemic cancer-directed therapy (yes or no) and type of therapy (chemotherapy vs immunotherapy vs targeted therapy).

Main Outcomes and Measures

Contact days (days with health care contact, outpatient or institution-based, outside the home) were identified through administrative data. The weekly percentage of contact days and fitted models with cubic splines were quantified to describe trajectories from diagnosis until death.

Results

A total of 5785 decedents with stage IV NSCLC were included (median age, 70 [IQR 62-77] years; 3108 [53.7%] were male, and 1985 [34.3%] received systemic therapy). The median overall survival was 108 (IQR, 49-426) days, median contact days were 36 (IQR, 21-62), and the median percentage that were contact days was 33.3%. A median of 5 (IQR, 2-10) days were spent with specialty palliative care. Patients who did not receive systemic therapy had a median overall survival of 66 (IQR, 34-130) days and median contact days of 28 (IQR, 17-44), of which a median of 5 (IQR, 2-9) days were spent with specialty palliative care. Overall and for subgroups, normalized trajectories followed a U-shaped distribution: contact days were most frequent immediately after diagnosis and before death. Patients who received targeted therapy had the lowest contact day rate during the trough (10.6%; vs immunotherapy, 15.4%; vs chemotherapy, 17.7%).

Conclusions and Relevance

In this cohort study, decedents with stage IV NSCLC had a median survival in the order of 3.5 months and spent 1 in every 3 days alive interacting with the health care system outside the home. These results highlight the need to better support patients and care partners, benchmark appropriateness, and improve care delivery.
Early Seizure Prophylaxis in Mild and Moderate Traumatic Brain Injury
Authors: Pease Matthew , Mittal Adi , Merkaj Sara , Okonkwo David O. , Gonzalez-Martinez Jorge A. , Elmer Jonathan , Liou Wen-Shyong , Pingue Valeria , Hammond Flora M. , Abramovici Sergiu , Castellano James , Barot Niravkumar
Published: April 2024

Importance

Guidelines recommend seizure prophylaxis for early posttraumatic seizures (PTS) after severe traumatic brain injury (TBI). Use of antiseizure medications for early seizure prophylaxis after mild or moderate TBI remains controversial.

Objective

To determine the association between seizure prophylaxis and risk reduction for early PTS in mild and moderate TBI.

Data Sources

PubMed, Google Scholar, and Web of Science (January 1, 1991, to April 18, 2023) were systematically searched.

Study Selection

Observational studies of adult patients presenting to trauma centers in high-income countries with mild (Glasgow Coma Scale [GCS], 13-15) and moderate (GCS, 9-12) TBI comparing rates of early PTS among patients with seizure prophylaxis with those without seizure prophylaxis.

Data Extraction and Synthesis

The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) reporting guidelines were used. Two authors independently reviewed all titles and abstracts, and 3 authors reviewed final studies for inclusion. A meta-analysis was performed using a random-effects model with absolute risk reduction.

Main Outcome Measures

The main outcome was absolute risk reduction of early PTS, defined as seizures within 7 days of initial injury, in patients with mild or moderate TBI receiving seizure prophylaxis in the first week after injury. A secondary analysis was performed in patients with only mild TBI.

Results

A total of 64 full articles were reviewed after screening; 8 studies (including 5637 patients) were included for the mild and moderate TBI analysis, and 5 studies (including 3803 patients) were included for the mild TBI analysis. The absolute risk reduction of seizure prophylaxis for early PTS in mild to moderate TBI (GCS, 9-15) was 0.6% (95% CI, 0.1%-1.2%; P = .02). The absolute risk reduction for mild TBI alone was similar 0.6% (95% CI, 0.01%-1.2%; P = .04). The number needed to treat to prevent 1 seizure was 167 patients.

Conclusion and Relevance

Seizure prophylaxis after mild and moderate TBI was associated with a small but statistically significant reduced risk of early posttraumatic seizures after mild and moderate TBI. The small absolute risk reduction and low prevalence of early seizures should be weighed against potential acute risks of antiseizure medications as well as the risk of inappropriate continuation beyond 7 days.
Prediction of immunochemotherapy response for diffuse largeB‐cell lymphoma using artificial intelligence digital pathology
Authors: Lee Jeong Hoon , Song Ga‐Young , Lee Jonghyun , Kang Sae‐Ryung , Moon Kyoung Min , Choi Yoo‐Duk , Shen Jeanne , Noh Myung‐Giun , Yang Deok‐Hwan
Published: April 2024

Diffuse large B‐cell lymphoma (DLBCL) is a heterogeneous and prevalent subtype of aggressive non‐Hodgkin lymphoma that poses diagnostic and prognostic challenges, particularly in predicting drug responsiveness. In this study, we used digital pathology and deep learning to predict responses to immunochemotherapy in patients with DLBCL. We retrospectively collected 251 slide images from 216 DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP), with their immunochemotherapy response labels. The digital pathology images were processed using contrastive learning for feature extraction. A multi‐modal prediction model was developed by integrating clinical data and pathology image features. Knowledge distillation was employed to mitigate overfitting on gigapixel histopathology images to create a model that predicts responses based solely on pathology images. Based on the importance derived from the attention mechanism of the model, we extracted histological features that were considered key textures associated with drug responsiveness. The multi‐modal prediction model achieved an impressive area under the ROC curve of 0.856, demonstrating significant associations with clinical variables such as Ann Arbor stage, International Prognostic Index, and bulky disease. Survival analyses indicated their effectiveness in predicting relapse‐free survival. External validation using TCGA datasets supported the model's ability to predict survival differences. Additionally, pathology‐based predictions show promise as independent prognostic indicators. Histopathological analysis identified centroblastic and immunoblastic features to be associated with treatment response, aligning with previous morphological classifications and highlighting the objectivity and reproducibility of artificial intelligence‐based diagnosis. This study introduces a novel approach that combines digital pathology and clinical data to predict the response to immunochemotherapy in patients with DLBCL. This model shows great promise as a diagnostic and prognostic tool for clinical management of DLBCL. Further research and genomic data integration hold the potential to enhance its impact on clinical practice, ultimately improving patient outcomes.
Non‐neurological factors associated with serum neurofilament levels in the United States population
Authors: Ramanathan Murali
Published: April 2024

Objective

To model interdependencies of serum neurofilament light chain (sNfL), a clinically useful biomarker of axonal injury in neurological diseases, with demographic, anthropometric, physiological, and disease biomarkers in the United States population.

Methods

sNfL and 80 biomarkers were obtained from the National Health and Nutrition Examination Survey (n = 2071, age: 20–75 years). Body habitus and composition, electrolytes, blood cell, metabolic, liver, and kidney function biomarkers, and common diseases were assessed with weighted regression adjusted for age, sex, and race/ethnicity. Salient biomarkers were modeled with ensemble learning; a Bayesian network structure was obtained for interdependencies.

Results

Age was strongly associated with sNfL. sNfL levels were 13% higher in men versus women. Mexican Americans had 18.5% lower sNfL versus Non‐Hispanic Whites. sNfL was similar in pregnant versus nonpregnant women. Lymphocyte, and neutrophil numbers, and phosphorus, and chloride levels were associated with sNfL. Multiple liver function (e.g., albumin and gamma‐glutamyltransferase), renal function (e.g., creatinine and urea), and carbohydrate/lipid metabolism markers (e.g., glucose and triglycerides) were associated with sNfL. A 50% greater creatinine was associated with 26.8% greater sNfL. Diabetes, kidney disease, congestive heart failure, and stroke were associated with sNfL. The ensemble learning algorithm predicted high sNfL outliers with 5.06%–9.16% test error. Bayesian network modeling indicated sNfL had neighbor dependencies with age, creatinine, albumin, and chloride.

Interpretation

sNfL is associated with age, kidney and liver function, diabetes, blood cell subsets, and electrolytes. sNfL may be a useful biomarker for biological age of the whole body and major organ systems including the brain.
Part 8 update: AATOD argues for removing more barriers to methadone treatment
Authors: Knopf Alison
Published: April 2024

Changes to the CFR 42 Part 8 regulations covering methadone treatment for opioid use disorder (OUD) have been welcomed by opioid treatment programs (OTPs) (see ADAW https://onlinelibrary.wiley.com/doi/10.1002/adaw.34023), which are the only providers with experience using methadone for this condition. However, the devils are, as always, in the details. It's not just a matter of the Substance Abuse and Mental Health Services Administration (SAMHSA) changing its rules.