bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial alignment of the mouse blastocyst axis across the first cleavage plane is caused by mechanical constraint rather than developmental bias among blastomeres
Authors: Alarcón Vernadeth B. , Marikawa Yusuke
Published: January 2008

The embryonic–abembryonic (Em–Ab) axis of the mouse blastocyst has been found in several studies to align orthogonal to the first cleavage plane, raising the possibility that a developmental prepattern already exists at the two‐cell stage. However, it is also possible that such alignment is not due to any developmental disparity between the two‐cell stage blastomeres, but rather is caused by an extrinsic mechanical constraint that is conferred by an irregular shape of the zona pellucida (ZP). Here, we conducted a series of experiments to distinguish between these possibilities. We showed that the shape of the ZP at the two‐cell stage varied among embryos, ranging from near spherical to ellipsoidal, and that the ZP shape did not change until the blastocyst stage. In those embryos with an ellipsoidal ZP, the Em–Ab axis tended to lie orthogonal to the first cleavage plane, while in those embryos with a near spherical ZP, there was no such relationship. The clonal boundary between the descendants of the two‐cell stage blastomeres tended to lie orthogonal to the Em–Ab axis when the rotation of the embryo within the ZP was experimentally prevented, while the control embryos did not exhibit such tendency. These results support the possibility that an apparent correlation between the first cleavage plane and the blastocyst axis can be generated by the mechanical constraint from the ZP but not by a developmental prepattern. Moreover, recent reports indicate that the vegetal blastomere of the four‐cell stage embryo that had undergone a specific type of second cleavages is destined to contribute to the abembryonic side of the blastocyst. However, our present study shows that in spite of such specific second cleavages, the vegetal blastomere did not preferentially give rise to the abembryonic side. This result implicates that the lineage of the four‐cell stage blastomere is not restricted even when embryos undergo a specific type of second cleavages. Mol. Reprod. Dev. 75: 1143–1153, 2008. © 2008 Wiley‐Liss, Inc.
Constitutive description of interface behavior including cyclic loading and particle breakage within the framework of critical state soil mechanics
Authors: Liu Huabei , Ling Hoe I.
Published: January 2008

The cyclic behavior of soil–structure interface can be very important in dynamic problems. The cyclic behavior of soil–structure interface may be nonlinear, which includes hysteresis, hardening, degradation, and particle breakage. The breakage of granular soil particles during shearing of granular soil–structure interface is associated with cyclic degradation and can be critical to the dynamic behavior of soil–structure system. The critical state soil mechanics concept formerly used to simulate the nonlinear monotonic behavior of granular soil–structure interface was modified and extended to describe the cyclic behavior, especially soil‐particle breakage and degradation during cyclic shearing. Soil‐particle breakage was assumed to relate to the energy consumption during cyclic shearing and the critical state line of the soil–structure interface was assumed to translate with the consumption of shearing energy during cyclic shearing as the threshold value is attained. The model was formulated in the framework of generalized plasticity and is capable of describing the salient features of granular soil–structure interface under cyclic loading. Most of the model parameters have straightforward physical meanings and are calibrated using monotonic or cyclic interface test results. The proposed model was calibrated and validated against published test results. The dependency of interface behavior on stress path and cyclic degradation can be successfully described by the proposed model. Copyright © 2008 John Wiley & Sons, Ltd.
Uniform convergence of the multigrid V‐cycle on graded meshes for corner singularities
Authors: Brannick James J. , Li Hengguang , Zikatanov Ludmil T.
Published: January 2008

This paper analyzes a multigrid (MG) V‐cycle scheme for solving the discretized 2D Poisson equation with corner singularities. Using weighted Sobolev spaces Kma(Ω) and a space decomposition based on elliptic projections, we prove that the MG V‐cycle with standard smoothers (Richardson, weighted Jacobi, Gauss–Seidel, etc.) and piecewise linear interpolation converges uniformly for the linear systems obtained by finite element discretization of the Poisson equation on graded meshes. In addition, we provide numerical experiments to demonstrate the optimality of the proposed approach. Copyright © 2008 John Wiley & Sons, Ltd.
Metaphors in qualitative research: Shedding light or casting shadows?
Authors: Carpenter Jacque
Published: January 2008

The use of metaphors in qualitative research provides an opportunity to examine phenomena from a unique and creative perspective. Metaphors can be used to provide structure to the data; to understand a familiar process in a new light; to identify situation‐specific interventions; and to evoke emotion. Misuse of metaphors may detract from the intended research message. Mixing metaphors, failing to follow through with metaphors, and using metaphors that do not fit the data can misrepresent the data. The choice to use metaphors should not become a self‐serving attempt at creativity that supersedes subject and substance. At their best, metaphors illuminate the meanings of experiences; at their worst, metaphors distort or obscure the essences of them. © 2008 Wiley Periodicals, Inc. Res Nurs Health 31:274–282, 2008
Histopathological and immunohistochemical characterization of canine prostate cancer
Authors: Lai Chen‐Li , van den Ham René , van Leenders Geert , van der Lugt Jaco , Mol Jan A. , Teske Erik
Published: January 2008

Background

In this study we try to identify the origin of canine prostate cancer (cPC) by classifying the tumors histological subtypes and relate these subtypes to their combined expressional characteristics of several tissue specific and differentiation markers.

Methods

cPCs were examined histomorphologically and by immunohistochemical detection of the cytokeratin markers CK14, HMWCK, CK5, CK18, and CK7, and of the markers UPIII, PSA and PSMA.

Results

Histopathologically, six growth patterns could be differentiated. The most frequent patterns were solid, cribriform and micropapillary growth patterns, while sarcomatoid, small acinar/ductal, and tubulo‐papillary growth patterns were less frequent present. Solid growth patterns were significantly (P = 0.027) more often seen in castrated dogs. Immunohistochemically, about half of the cPC cases showed expression of PSA (8/20) and PSMA (10/20); 85% and 60% of the cPC expressed UPIII (17/20) and CK7 (12/20), while 13 and 12 cPC expressed CK5 and CK14, respectively; all cPC expressed CK18. CK14 was significantly more often and UPIII less frequent expressed in the solid growth patterns than in the micropapillary and cribriform patterns, respectively.

Conclusions

Canine prostate cancer appear to be more aggressive and of a less differentiated type than most common human prostate cancers. Comparing the expression patterns of the markers in cPC to those in normal canine prostate tissue, cPC most likely originates from the collecting ducts rather than from the peripheral acini. Given also the fact that canine prostate cancer is unresponsive to androgen withdrawal therapy, canine prostate cancer mostly resembles human, androgen refractory, poorly differentiated prostate cancer. Prostate 68: 477–488, 2008. © 2008 Wiley‐Liss, Inc.
Obsidian hydration dating by SIMS‐SS: Surface suitability criteria from atomic force microscopy
Authors: Liritzis I. , Bonini M. , Laskaris N.
Published: January 2008

Obsidian artefacts used by prehistoric people could be dated by the SIMS‐SS method. However, the method contains some limitations regarding the degree of smoothness of the surface. The presence of wells, cracks, pits, crystals and/or crests induce errors in the dating. Here, we briefly introduce the SIMS‐SS method and provide first images of the atomic force microscopy (AFM) of obsidian surfaces and discuss the impact of AFM results on the SIMS‐SS dating. The presented dating is straightforward for flat regular surfaces and problematic for irregular surfaces. Copyright © 2008 John Wiley & Sons, Ltd.
Capture-avoiding substitution as a nominal algebra
Authors: Gabbay Murdoch J. , Mathijssen Aad
Published: January 2008

Substitution is fundamental to the theory of logic and computation. Is substitution something that we define on syntax on a case-by-case basis, or can we turn the idea of substitution into a mathematical object? We give axioms for substitution and prove them sound and complete with respect to a canonical model. As corollaries we obtain a useful conservativity result, and prove that equality-up-to-substitution is a decidable relation on terms. These results involve subtle use of techniques both from rewriting and algebra. A special feature of our method is the use of nominal techniques. These give us access to a stronger assertion language, which includes so-called ‘freshness’ or ‘capture-avoidance’ conditions. This means that the sense in which we axiomatise substitution (and prove soundness and completeness) is particularly strong, while remaining quite general.
Long‐term Result of Total versus Partial Fundoplication after Esophagomyotomy for Primary Esophageal Motor Disorders
Authors: Zhu Zi‐Jiang , Chen Long‐Qi , Duranceau Andre
Published: January 2008

Background

The selection of the type of fundoplication or the necessity for an added fundoplication after esophagomyotomy (Heller’s operation) for the treatment of achalasia remains controversial. The present retrospective study was designed to compare the long‐term results of total and partial fundoplication on the myotomized esophagus.

Methods

Between 1978 and 1998, a total of 64 consecutive patients with achalasia or diffuse esophageal spasm underwent esophagomyotomy and an antireflux operation via a left thoracotomy approach. Twenty‐one had a total fundoplication (Nissen Group) during the period 1978–1983. After 1984 and until 1998, the remaining 43 patients were treated with addition of a Belsey Mark IV partial fundoplication (Belsey Group) to protect the myotomized esophagus. Clinical, radiologic, radionuclide transit, manometric, 24–h pH monitoring, and endoscopic assessments were obtained before and after the operation.

Results

There were no operative deaths or major complications in either group. After 6 years of follow‐up the Belsey group was compared to the Nissen group. A higher frequency of dysphagia (7/18 versus 3/31; p = 0.025), more barium stasis (9/13 versus 10/27; p = 0.056), and increased radionuclide material retention (52.4% versus 29.2%; p = 0.044) were observed in the Nissen group. These findings were confirmed by endoscopy, which showed increased esophageal lumen dilation (10/15 versus 8/26; p = 0.026) and more frequent food retention (11/15 versus 6/26; p = 0.002). Functionally, both operations successfully reduced the lower esophageal sphincter pressure gradient (from 23.8 to 7.7 mmHg for the Nissen group, and from 27.4 to 8.2 mmHg for the Belsey group; p = 0.656). In the Nissen group, the esophageal diameter observed on radiology increased from 3.9 cm preoperatively to 5.5 cm postoperatively (p = 0.012), whereas it remained identical for the Belsey group (ranging from 5.4 cm to 5.3 cm; p = 0.695). Reoperation to relieve recurrent dysphagia and esophageal retention was necessary in 8 patients from the Nissen group and in 1 patient from the Belsey group (p < 0.001).

Conclusions

When treating achalasia or diffuse esophageal spasm by esophageal myotomy and an antireflux operation, a total fundoplication adds too much resistance to allow esophageal emptying and is considered as inappropriate. A partial fundoplication provides proper antireflux effects without causing significant esophageal emptying difficulties.
Surgery for Cushing’s Syndrome: An Historical Review and Recent Ten‐year Experience
Authors: Porterfield John R. , Thompson Geoffrey B. , Young William F. , Chow John T. , Fryrear Raymond S. , van Heerden Jon A. , Farley David R. , Atkinson John L. D. , Meyer Fredric B. , Abboud Charles F. , Nippoldt Todd B. , Natt Neena , Erickson Dana , Vella Adrian , Carpenter Paul C. , Richards Melanie , Carney J. Aidan , Larson Dirk , Schleck Cathy , Churchward Marilyn , Grant Clive S.
Published: January 2008

Background

Cushing’s syndrome (CS), due to multiple etiologies, is a disorder associated with the ravages of cortisol excess. The purpose of this review article is to provide a historical synopsis of surgery for CS, review a recent 10‐year period of operative management at a tertiary care facility, and to outline a practical approach to diagnosis and management.

Materials and Methods

From 1996 to 2005, 298 patients underwent 322 operative procedures for CS at Mayo Clinic, Rochester, Minnesota. A retrospective chart review was carried out. Data was gathered regarding demographics, preoperative assessment, procedures performed, and outcomes. Data are presented as counts and percentages. Five‐year survival rates were calculated where applicable by the Kaplan‐Meier method. Statistical analysis was carried out with SAS, version 9 (SAS Institute, Inc., Cary, NC).

Results

Two‐hundred thirty‐one patients (78%) had ACTH‐dependent CS and 67 patients (22%) had ACTH‐independent CS. One‐hundred ninety‐six patients (66%) had pituitary‐dependent CS and 35 patients (12%) had ectopic ACTH syndrome. Fifty‐four patients (18%) had cortisol‐secreting adenomas, 10 patients (3%) had cortisol‐producing adrenocortical carcinomas, and 1% had other causes. Cure rates for first time pituitary operations (transsphenoidal, sublabial, and endonasal) were 80% and 55% for reoperations. Most benign adrenal processes could be managed laparoscopically. Five‐year survival rates (all causes) were 90%, 51%, and 23% for adrenocortical adenomas, ectopic ACTH syndrome, and adrenocortical carcinomas, respectively.

Conclusions

Surgery for CS is highly successful for pituitary‐dependent CS and most ACTH‐independent adrenal causes. Bilateral total adrenalectomy can also provide effective palliation from the ravages of hypercortisolism in patients with ectopic ACTH syndrome and for those who have failed transsphenoidal surgery. Unfortunately, to date, adrenocortical carcinomas are rarely cured. Future successes with this disease will likely depend on a better understanding of tumor biology, more effective adjuvant therapies and earlier detection. Clearly, IPSS, advances in cross‐sectional imaging, along with developments in transsphenoidal and laparoscopic surgery, have had the greatest impact on today’s management of the complex patient with CS.
Prediction of Response to Splenectomy in Patients with Idiopathic Thrombocytopenic Purpura
Authors: Shojaiefard A. , Mousavi S. A. , Faghihi S. H. , Abdollahzade S.
Published: January 2008

Background

Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by destruction of opsonized platelets in the reticuloendothelial system, particularly the spleen, and by resulting low platelet counts. Splenectomy is the standard second‐line treatment for patients with ITP who do not respond to corticosteroids. In the present study we determined predictive factors for the response of patients with ITP to splenectomy.

Materials and Methods

For thirty‐one patients with ITP referred from the Hematology Department of Shariati Hospital, open surgical splenectomy was performed between February 2002 and December 2004. All potentially important variables of response were collected and analyzed to determine predictive parameters.

Results

Older patients (>52) responded less positively than younger patients (<52) to splenectomy (p < 0.01). Likewise, patients with a sustained remission after splenectomy had a significantly shorter interval of diagnosis of ITP to splenectomy (p < 0.05) and shorter duration of corticosteroid therapy before splenectomy (p < 0.05).

Conclusions

This study confirms that splenectomy is an effective treatment for patients with ITP. Our findings highlight age as the major predictive factor of long‐term response to splenectomy in patients with ITP.
Myopathy in Gaucher disease
Authors: Tsai Li‐Kai , Chien Yin‐Hsiu , Yang Chih‐Chao , Hwu Wuh‐Liang
Published: January 2008

Gaucher disease is a recessively inherited lysosomal storage disorder, caused by deficiency of glucocerebrosidase activity. Affected individuals usually present with hepatosplenomegaly, anaemia, thrombocytopenia, and skeletal diseases. A wide range of neurological manifestations have also been recognized in Gaucher patients including acute neurological deterioration in infancy, mental retardation, ocular motor apraxia, seizure, and parkinsonism. Although muscle weakness is not an uncommon finding in patients with Gaucher disease, the aetiology of weakness is not well understood. We prospectively investigated seven Gaucher patients and found that four of them (patients 1–4) had mild to moderate degree of proximal‐predominant symmetrical muscle weakness in four limbs. By history, three patients (patients 1–3) developed insidious onset of nonprogressive muscle weakness in four limbs with easy muscle fatigue from adolescence. A needle electromyographic study detected some small, brief polyphasic waves in these four patients. Muscle biopsy in one patient (patient 1) showed a few atrophic type II muscle fibres without infiltration of Gaucher cells. Three patients (patients 1–3) continuously received enzyme replacement therapy with imiglucerase and their muscle strength seemed improved after two years. We concluded that Gaucher disease may be associated with myopathy.
Specialized host‐plant performance of the cotton aphid is altered by experience
Authors: Liu Xiang Dong , Zhai Bao Ping , Zhang Xiao Xi
Published: January 2008

Although distinct host specialization is observed for the cotton‐melon aphid (Aphis gossypii Glover) on cotton and cucurbit plants, it is still ambiguous whether the specialization is altered by experience on a novel host plant. Here the performance of cotton and cucurbit‐specialized aphids, A. gossypii on novel host plants was studied by a host‐selection test and by the life‐table method. The two host‐specialized aphids cannot survive and establish populations after reciprocal host transfers. They have ability to recognize the host plants on which they were reared, and escape behavior from novel hosts was observed. Interestingly, the cotton and cucurbit‐specialized aphids survive and reproduce normally on hibiscus (Hibiscus syriacus), a main overwintering host plant, and host‐fidelity of A. gossypii to cucurbit plants is altered by feeding and living experience on hibiscus, which confers the same capacity to use cotton and cucumber on to the cucurbit‐specialized population, but host‐fidelity to cotton is not altered and the fitness of the cotton specialized population to cucumber is still poorer. A. gossypii from hibiscus has a significant preference for cotton to cucumber in the host‐selection process, and none stays on cucumber more than 20 h after transfer. The results presented imply that cucurbit‐specialized aphids might not return to an overwintering host plant (hibiscus) in wild fields, so host conservatism to cucurbit plants is maintained. The potential of cucurbit‐specialized aphids of A. gossypii to use cotton plants, intermediated by experience on hibiscus, suggests that the specialized host‐plant performance of phytophagous insects is not wholly conservative.
Microwave Synthesis of Cationic Fatty Imidazolines and their Characterization
Authors: Bajpai Divya , Tyagi V. K.
Published: January 2008

This paper describes an efficient method for the synthesis of long chain dialkyldiamido imidazolines by the reaction of diethylenetriamine and several fatty acids under non‐solvent microwave irradiation using calcium oxide as support This synthesis required much less time in comparison to conventional thermal condensation and is carried out in an open vessel and the products obtained by this method were found to be in good yields and of high purity. Fatty imidazolines were then quaternized by using dimethyl sulfate as a quaternizing agent and isopropanol as a solvent, to produce cationic imidazolinium salts which were evaluated for yield and cationic content. The instrumental techniques, viz. FT‐IR and 1H NMR verified the formation of imidazolines and its subsequent quaternization. This method produced imidazolines in the very low time of 5–10 min and gave a yield of 89–91% as compared to a very long time of 8–10 h and a lower yield of 75–80% by the conventional thermal condensation method.
A high resolution SEM study of the effects of RU486, used as a postcoital contraceptive, on the rat uterus during early pregnancy
Authors: Scholtz Kathrine E. , Penny Clem B. , Hosie Margot J.
Published: January 2008

During the window of receptivity, a narrow range of time under the control of the ovarian hormones progesterone and oestrogen, when a blastocyst can attach to the uterine surface, the plasma membrane of the uterine epithelial cells undergoes a remarkable change in structure, known as ‘the plasma membrane transformation’ of early pregnancy. RU486, the controversial abortion drug (Mifegyne™), acts as a progesterone receptor antagonist, resulting in transcriptionally inactive progesterone receptors. In view of this, a change in the well‐documented sequences of the plasma membrane transformation is postulated. This study therefore aims to investigate the effects of RU486 on this sequence of events in the implantation and non‐implantation sites of the rat uterus. In both RU486 treated and control animals, on days 4.5, 5.5 and 6.5 of pregnancy, scanning electron microscopy revealed a distinct pattern of folding of the uterine surface in non‐implantation sites. In contrast, folding was not observed within the implantation sites. These results indicate that surface alterations are probably not under the control of progesterone signalling. The lack of folding at the implantation sites possibly ensures maximum close contact between the blastocyst and the maternal tissue thus promoting implantation. During early pregnancy, specifically on day 5.5, the microvilli of the uterine epithelial cells in the treated animals were more dense than those in the untreated animals. Such microvilli are characteristic of the uterine epithelial cells of a uterus under‐stimulated by hormones. Flattening of the apical cell borders usually seen at the time of blastocyst attachment and implantation was not observed following RU486 treatment. Large apical protrusions were observed in the RU486 treated animals only, possibly linked in someway to apoptosis. The antiprogestin properties of RU486 may further elucidate the progesterone effects associated with early pregnancy.
Differentiation of embryonic stem cells towards pancreatic progenitor cells and their transplantation into streptozotocin‐induced diabetic mice
Authors: Chen Chunhua , Zhang Yuebo , Sheng Xiaoyan , Huang Cheng , Zang Ying Qin
Published: January 2008

Type I diabetes is characterized by the deficiency of endocrine β cells in the pancreatic islets of Langerhans and transplantation of islet cells can be an effective therapeutic approach. Embryonic stem cells can be differentiated into any cell type, and therefore represent an unlimited source of islet cells for the transplantation and treatment for type I diabetes. We have adopted an easy and reproducible in vitro differentiation system with a reduced serum concentration plus nicotinamide to generate early pancreatic progenitor cells from embryonic stem cells. Gene expression analysis indicated that the differentiated cells expressed not only endoderm markers such as GATA‐4, HNF‐3β, but also early markers of pancreatic development including key transcription factors PDX‐1 and IAPP. Some pancreatic specific markers, such as insulin I, insulin II, Glu‐2 and glucagon, were also expressed to some extent at the mRNA level. Differentiated ES cells showed low level immunoreactivity for insulin. However, transplantation of these early pancreatic progenitor clusters into STZ‐induced diabetic mice failed to reverse the hyperglycemic state of the disease as reported previously. The results suggest that culture manipulation can direct ES cells to differentiate into early pancreatic progenitor cells committing to pancreatic islet cell fate, but these cells cannot function normally to reduce blood glucose of diabetic mice at this stage.
Behavioral effects of current Alzheimer's disease treatments: A descriptive review
Authors: Cummings Jeffrey L. , Mackell Joan , Kaufer Daniel
Published: January 2008

Background

Behavioral abnormalities and neuropsychiatric symptoms are common manifestations of Alzheimer's disease (AD). Many clinical trials of cholinesterase inhibitors (ChE‐Is) and memantine have included behavioral measures as primary or secondary outcomes, and most have observed behavioral benefits in conjunction with treatment. The purpose of this review was to determine the frequency of positive behavioral outcomes in AD clinical trials and clinical reports, to determine the symptoms most responsive to antidementia agents, and to explore factors that correlate with negative outcomes in clinical trials of antidementia agents with regard to behavioral measures.

Methods

We performed a computerized search of randomized clinical trials and open‐label studies of ChE‐Is and memantine for AD including a behavioral outcome measure. Studies involving 10 or more patients using therapeutic doses of the target agents and including a behavioral measure as a primary or secondary outcome were included in this review.

Results

One hundred fifty‐seven peer‐reviewed articles and 68 publicly presented abstracts were identified in the literature search. Subsequent review established that 15 publications arising from 13 randomized, double‐blind, placebo‐controlled AD trials met the review inclusion criteria. Positive outcomes on behavioral measures were reported in 8 of 15 publications as a primary or secondary outcome. In most blinded AD clinical trials, behavioral measures were secondary outcomes. Mood symptoms and apathy have most commonly responded to ChE‐Is, whereas memantine has been associated with a reduction in irritability and agitation. However, there is substantial variability among trials in terms of behavioral outcomes. Studies that assessed patients with more severe dementia, included patients with less severe behavioral disturbances at baseline, involved institutionalized patients, or were international in scope tended to have negative outcomes. In institutionalized patients there is commonly an improvement in the placebo group that confounds the observation of any drug‐placebo difference.

Conclusions

Antidementia agents have been associated with beneficial behavioral outcomes in many randomized clinical trials and open‐label studies. Most studies are not designed to test the psychotropic properties of antidementia drugs. Trials with negative behavioral outcomes are most likely to involve patients who are institutionalized and have few behavioral disturbances at baseline. Clinical trials designed to assess behavioral effects of antidementia agents should anticipate these factors.
Differentiating Alzheimer's disease from dementia with Lewy bodies and Parkinson's disease with (+)‐[11C]dihydrotetrabenazine positron emission tomography
Authors: Koeppe Robert A. , Gilman Sid , Junck Larry , Wernette Kris , Frey Kirk A.
Published: January 2008

Background

Several progressive neurologic disorders begin with cognitive decline or parkinsonism, notably Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy bodies (DLB). We used positron emission tomography (PET) in attempts to differentiate these disorders.

Methods

We performed PET with (+)‐[11C]dihydrotetrabenazine ([11C]DTBZ) to examine blood‐to‐brain ligand transport (K1) and striatal monoaminergic presynaptic binding (distribution volume [DV]) in 25 DLB, 30 PD, and 25 AD patients and 57 elderly controls (NC).

Results

[11C]DTBZ DV was decreased significantly in caudate nucleus, anterior putamen, and posterior putamen in DLB and PD compared with AD and NC. DLB and PD groups showed an anterior‐to‐posterior gradient of binding loss relative to NC, least in caudate nucleus and largest in posterior putamen. The gradient was significantly steeper in PD than DLB. Both PD and DLB showed significantly greater interhemispheric striatal binding asymmetry than NC, and PD had greater asymmetry than DLB. Cerebral cortical [11C]DTBZ K1 was decreased diffusely by 4% to 8% in PD. Larger K1 deficits occurred in AD and DLB temporoparietal and prefrontal association cortices and posterior cingulate cortex. Greater reduction of K1 occurred in occipital cortex in DLB than AD. Receiver operating characteristic curve analyses distinguished DLB from AD more effectively on the basis of striatal DV than occipital K1 and distinguished DLB from PD more effectively on the basis of cerebral cortical K1 than striatal DV patterns. Overall, 90% of cases were properly classified by combining these measures.

Conclusions

PET with [11C]DTBZ can differentiate DLB from both PD and AD in a single neuroimaging study.
The pre–mild cognitive impairment, subjective cognitive impairment stage of Alzheimer's disease
Authors: Reisberg Barry , Prichep Leslie , Mosconi Lisa , John E. Roy , Glodzik‐Sobanska Lidia , Boksay Istvan , Monteiro Isabel , Torossian Carol , Vedvyas Alok , Ashraf Nauman , Jamil Imran A. , de Leon Mony J.
Published: January 2008

Background

Subjective cognitive impairment (SCI) has been a common, but poorly understood condition, frequently occurring in older persons.

Methods

The past and the emerging literature on SCI and synonymously named conditions is reviewed.

Results

Findings include: (1) There is support from at least one longitudinal study for a long‐standing concept of SCI as a pre–mild cognitive impairment (MCI) condition lasting ∼15years. (2) There are complex relationships between SCI and depression and anxiety. (3) Differences in SCI subjects from age‐matched non‐SCI persons are being published in terms of cognitive tests, hippocampal gray matter density, hippocampal volumes, cerebral metabolism, and urinary cortisol levels. Psychometric and dementia test score differences between SCI and MCI subjects have long been evident. (4) Predictive electrophysiologic features of subsequent decline in SCI subjects are being published.

Conclusions

Studies of therapeutic agents in SCI treatment and resultant Alzheimer's disease prevention appear to be feasible. These trials are also necessary from a public health perspective.
Prognostic value of Bcl‐2 in breast cancer patients treated with neoadjuvant anthracycline based chemotherapy
Authors: Vargas-Roig Laura M. , Cuello-Carrión F. Darío , Fernández-Escobar Nicolás , Daguerre Pedro , Leuzzi Marcela , Ibarra Jorge , Gago Francisco E. , Nadin Silvina B. , Ciocca Daniel R.
Published: January 2008

We have analyzed the predictive/prognostic value of Bcl‐2 protein in breast cancer patients treated with neoadjuvant chemotherapy. One hundred and ten patients were submitted to two different chemotherapeutic regimens: a) 5‐fluorouracil, adriamycin or epirubicin, and cyclophosphamide (FAC/FEC) during 2–6 cycles before surgery and 3 or 4 additional cycles of FAC/FEC after surgery (n=40) and b) doxorubicin (D) 75mg/m2 or epirubicin (E) 120mg/m2 during 4 cycles before surgery, and 6 cycles of cyclophosphamide, methotrexate, and 5‐fluorouracil (CMF) after surgery (n=70). Bcl‐2 expression, evaluated by immunohistochemistry, did not change significantly after chemotherapy and was not related to clinical/pathological response. In FAC/FEC group, Bcl‐2 positive expression after chemotherapy correlated with better disease free survival (DFS) and overall survival (OS) (P=0.008 and P=0.001). In D/E group, Bcl‐2 also correlated with better DFS and OS (P=0.03 and P=0.054) in the post‐chemotherapy biopsies. An unusual nuclear localization of Bax was observed in some biopsies, but this localization did not correlate with the tumor response or outcome of the patients. We found that a high Bcl‐2 expression had no predictive value but had prognostic value in breast cancer patients treated with neoadjuvant anthracycline based chemotherapy.
The association between dietary macronutrient intake and the prevalence of the metabolic syndrome
Authors: Skilton Michael R. , Laville Martine , Cust Anne E. , Moulin Philippe , Bonnet Fabrice
Published: January 2008

We examined the association of dietary carbohydrates, protein, fat (including fatty acid subtypes) and alcohol with the metabolic syndrome and its components, in a cross-sectional study of 1626 patients with at least one cardiovascular risk factor. Multivariate nutrient density substitution models were used to examine the associations between macronutrients (assessed by 24 h dietary recall) and the metabolic syndrome. These models express the effects of ‘substituting’ one macronutrient for another without altering total energy intake. Increases in carbohydrates offset by isoenergetic decreases in either fat or protein were associated with a decrease in the prevalence of the metabolic syndrome (OR 0·87 (95 % CI 0·81, 0·93), P < 0·0001; OR 0·70 (95 % CI 0·61, 0·79), P < 0·0001, per 5 % energy intake respectively). Increased intake of dietary fat at the expense of dietary protein was also associated with a decreased prevalence of the metabolic syndrome (OR 0·80 (95 % CI 0·70, 0·92), P = 0·002 per 5 % energy intake). There were no statistically significant differences between fatty acid subtypes (P>0·10). Consumption of up to one standard alcoholic drink per d was associated with a lower prevalence of the metabolic syndrome when compared with non-drinkers (OR 0·67 (95 % CI 0·50, 0·89), P = 0·006); however, these benefits were weakened with higher levels of alcohol intake (P = 0·10 for one to three drinks and P = 0·29 for >three drinks). Thus, a diet high in carbohydrates, low in fat and protein, with low-to-moderate alcohol intake, is associated with a reduced prevalence of the metabolic syndrome.
Adaptation of calcium absorption during treatment of nutritional rickets in Nigerian children
Authors: Oramasionwu Gloria E. , Thacher Tom D. , Pam Sunday D. , Pettifor John M. , Abrams Steven A.
Published: January 2008

Nutritional rickets in Nigerian children has been effectively treated with Ca supplementation. High values of Ca absorption efficiency have been observed in untreated children, but whether Ca absorption efficiency changes during treatment with Ca is unknown. Our objective in conducting this study was to identify the effect of Ca therapy on Ca absorptive efficiency in children with primary Ca-deficient nutritional rickets. Twelve children with radiographically active rickets, 2 to 14 years of age (median 39 months) participated in the study. We assessed dietary Ca intake via dietary recalls, and measured biochemical markers of Ca and vitamin D homeostasis. Fractional Ca absorption was measured using a dual tracer stable isotope method, before and after 2 weeks of treatment with 15·0 mmol elemental Ca daily. Ten children had adequate urine collection for inclusion in the analysis. Usual dietary Ca intake was 4·2 (sd 1·0) mmol/d. The median Ca absorption prior to treatment was 72 % (range 52–97 %) and decreased significantly to 57 % (31–84 %) (P = 0·004) after 2 weeks of supplementation. We conclude that Nigerian children with rickets adapt to Ca supplementation with a small decrease in Ca absorptive capacity, but retain very high absorptive levels during supplementation. Overall Ca absorption efficiency was comparable with that identified in other populations with low Ca intakes. These data demonstrate that although absorptive capacity is regulated by supplementation, recovery from rickets likely occurs through efficient use of both dietary and supplemental Ca.
Law and Loss: Response to Catastrophein Numbers 15
Authors: Novick Tzvi
Published: January 2008

The episode of the wood-gatherer () in Num 15:32–36 is concisely narrated. The Israelites, in the wilderness, catch a man gathering wood on the Sabbath. They convey him to Moses and the congregation, evidently for judgment, but they cannot determine what his fate should be. A watch is therefore set over him until the matter can be clarified. Then God, presumably in response to an inquiry by Moses, informs him that the prisoner is to be stoned. The congregation forthwith executes the judgment. The story is sharply demarcated, on the one side by the law concerning unintentional and intentional sins (15:22–31)and on the other by the law of tassels (15:37–41). The present essay offers an interpretation of this story that situates it meaningfully in its current literary context and in the historical milieu in which it was redacted. I shall argue that the episode of the wood-gatherer addresses the force of covenantal law in the aftermath of national catastrophe.
Gift-Giving and Friendship: Seneca and Paul in Romans 1–8 on the Logic of God's Χάριϛ and Its Human Response
Authors: Engberg-Pedersen Troels
Published: January 2008

In this article I aim to address two questions that might initially appear independent, but are really connected. One is about twentieth century thought, the other is about Paul. Seneca will act as a mediator between the two.
Key issues for attention from ecological economists
Authors: EHRLICH PAUL R.
Published: January 2008

This paper gives an ecologist's overview of the deteriorating environmental situation. It then describes areas where the activities of ecological economists seem appropriate (e.g., ecosystem service valuation, trade) and others requiring more attention (e.g., definitions of utility, social discounting, preserving population diversity, global toxification, the epidemiological environment, overpopulation, overconsumption, the economic impacts of nuclear explosions, and the equilibration of opportunity costs when attempting to solve global dilemmas). A general problem is the failure of ecological economists adequately to communicate their results and concerns to the general public and to decision makers. In view of the demonstrable failure of traditional economics to focus its attention on what will be the central issues of the twenty-first century, it is clear that ecological economics is in a position to become the central subdiscipline of economics. In order to do so, it is important for ecological economists to always keep the ‘big picture’ in view.
Query evaluation and optimization in the semantic web
Authors: RUCKHAUS EDNA , RUIZ EDUARDO , VIDAL MARÍA-ESTHER
Published: January 2008

We address the problem of answering Web ontology queries efficiently. An ontology is formalized as adeductive ontology base(DOB), a deductive database that comprises the ontology's inference axioms and facts. A cost-based query optimization technique for DOB is presented. A hybrid cost model is proposed to estimate the cost and cardinality of basic and inferred facts. Cardinality and cost of inferred facts are estimated using an adaptive sampling technique, while techniques of traditional relational cost models are used for estimating the cost of basic facts and conjunctive ontology queries. Finally, we implement a dynamic-programming optimization algorithm to identify query evaluation plans that minimize the number of intermediate inferred facts. We modeled a subset of the Web ontology language Lite as a DOB and performed an experimental study to analyze the predictive capacity of our cost model and the benefits of the query optimization technique. Our study has been conducted over synthetic and real-world Web ontology language ontologies and shows that the techniques are accurate and improve query performance.
Impact of daily fluctuations on long‐term predictability of the Atlantic meridional overturning circulation
Authors: von Storch J.‐S. , Haak H.
Published: January 2008

The first continuous assessment of the Atlantic meridional overturning circulation (MOC) indicates strong MOC variability on time scales of about a few weeks. A large part of this variability results from, or is related to, wind stress forcing, which is not predictable beyond a few weeks. The presence of short‐term MOC fluctuations could significantly limit long‐term MOC predictability which owes its potential to the slow components in ocean dynamics. To quantify this limitation, two null hypotheses that address not only the existence but also the strength of slow dynamics are tested. Daily and yearly MOC time series generated by the ECHAM5/MPI‐OM model are used for this purpose. The tests compare the variance generated by slow dynamics with that of short‐terms fluctuations that extend into low frequencies. The comparison is done for total variances as well as for variances within different low‐frequency ranges. It is found that the model's slow dynamics become noticeable only on time scales longer than three years. The variance generated by the slow dynamics dominate that related to the low‐frequency extension of unpredictable noise only on time scales longer than 10 years. In order to utilize the potential predictability originating from slow processes, a prediction should correctly capture slow processes in the initial state by assimilating observations over a period of at least three years.
Observations of mixed layer restratification by onshore surface transport following wind reversal in a coastal upwelling region
Authors: Dale A. C. , Barth J. A. , Levine M. D. , Austin J. A.
Published: January 2008

Observations, from the Oregon continental shelf, describe the slumping of a coastal upwelling front in response to a reversal of winds from upwelling‐ to downwelling‐favorable. Initially, the front outcropped in a surface mixed layer of depth 10–20 m with a pronounced cross‐shelf density gradient. Following wind reversal, both the unbalanced cross‐shelf pressure gradient and wind‐driven Ekman transport drove a rapid onshore movement of near‐surface water, causing the mixed layer to restratify. At the surface, the cross‐shelf density gradient steepened to become a discontinuous front, which propagated onshore at 0.43–0.60 m s−1 as the head of a buoyant gravity current. Internal waves were driven ahead of the front on the base of the former mixed layer. An injected dye tracer revealed that surface water from inshore of the strongest frontal gradient detached from the surface as the gravity current passed over the top of it. This water largely retained the low potential vorticity signature that it had taken on in the mixed layer as it spread across the shelf in a weakly stratified, subsurface layer. Restratification and frontogenesis were most likely gravity‐driven in the first hours following wind reversal, with the contribution from Ekman transport becoming increasingly significant.
Deciphering the β‐adrenergic response in human embryonic stem cell‐derived‐cardiac myocytes: closer to clinical use?
Authors: Catalucci D , Bang M L , Condorelli G
Published: January 2008

Human embryonic stem cells (hESCs) are a pluripotent cell type considered to have high potential for the treatment of cardiovascular disease by cell replacement therapies. Several groups have shown that hESCs can be differentiated in vitro into cardiac myocytes, which may be used to facilitate tissue regeneration by injection directly into damaged myocardium. However, several hurdles still need to be overcome before these cells can be used in clinical trials. In particular, because transplanted hESC‐cardiac myocytes should integrate fully within the damaged heart, these cells must be functionally compatible with the host myocardium. To assess this aspect of hESC‐cardiac myocytes, Brito‐Martins et al. (2008) in this issue of the BJP, describe the responses of hESC‐cardiac myocytes to β‐adrenoceptor stimulation, compared to those of myocytes from adult human hearts. Data obtained using specific β‐adrenoceptor agonists showed good compatibility of hESC‐cardiac myocytes with adult human myocardium in terms of β‐adrenoceptor response.

British Journal of Pharmacology (2008) 153, 625–626; doi:10.1038/sj.bjp.0707633; published online 14 January 2008
ATL‐1, an analogue of aspirin‐triggered lipoxin A4, is a potent inhibitor of several steps in angiogenesis induced by vascular endothelial growth factor
Authors: Cezar‐de‐Mello P F T , Vieira A M , Nascimento‐Silva V , Villela C G , Barja‐Fidalgo C , Fierro I M
Published: January 2008

Background and purpose:

Vascular endothelial growth factor (VEGF) is the most important proangiogenic protein. We have demonstrated that ATL‐1, a synthetic analogue of aspirin‐triggered lipoxin A4, inhibits VEGF‐induced endothelial cell (EC) migration. In the present study, we investigated the effects of ATL‐1 in several other actions stimulated by VEGF.

Methods:

Human umbilical vein ECs were treated with ATL‐1 for 30 min before stimulation with VEGF. Cell proliferation was measured by thymidine incorporation. Adherent cells were determined by fluorescence intensity using a Multilabel counter. Expression and activity of matrix metalloproteinases (MMP) were analysed by western blot and zymography.

Key results:

ATL‐1 inhibited EC adhesion to fibronectin via interaction with its specific receptor. Furthermore, VEGF‐induced MMP‐9 activity and expression were reduced by pretreatment with ATL‐1. Because the transcription factor NF‐κB has been implicated in VEGF‐mediated MMP expression and EC proliferation, we postulated that ATL‐1 might modulate the NF‐κB pathway and, indeed, ATL‐1 inhibited NF‐κB nuclear translocation. Pretreatment of EC with ATL‐1 strongly decreased VEGF‐dependent phosphorylation of phosphainositide 3‐kinase (PI3‐K) and extracellular signal‐regulated kinase‐2 (ERK‐2), two signalling kinases involved in EC proliferation. Inhibition of VEGF‐induced EC proliferation by ATL‐1 was antagonized by sodium orthovanadate, suggesting that this inhibitory activity was mediated by a protein tyrosine phosphatase. This was confirmed by showing that ATL‐1 inhibition of VEGF receptor‐2 (VEGFR‐2) phosphorylation correlates with SHP‐1 association with VEGFR‐2.

Conclusions and implications:

The synthetic 15‐epi‐lipoxin analogue, ATL‐1, is a highly potent molecule exerting its effects on multiple steps of the VEGF‐induced angiogenesis.

British Journal of Pharmacology (2008) 153, 956–965; doi:10.1038/sj.bjp.0707650; published online 14 January 2008
The utility of biomarker discovery approaches for the detection of disease mechanisms in psychiatric disorders
Authors: Schwarz E , Bahn S
Published: January 2008

Schizophrenia remains an elusive multifaceted disorder with all evidence of its onset and aetiology pointing to a complex interplay of genetic, nutritional, environmental and developmental factors. Although several molecular and structural abnormalities have been reported for schizophrenia, no diagnostic test or other application of clinical use has yet emerged from this research. The heterogeneity of schizophrenia symptoms and its similarity to other psychiatric disorders, the accessibility of appropriate samples and the complexity of molecular alterations have greatly slowed down research. Biomarker discovery approaches should ultimately facilitate objective diagnosis, allow the identification of at‐risk individuals, predict treatment success and revolutionize drug‐discovery approaches. For psychiatric disorders, large sample numbers are necessary if disease‐intrinsic alterations are to be detected in an environment of high biological variability. Only recent technological advances facilitate the profiling of proteins and metabolites of large sample numbers. These approaches promise to provide interesting insights into disease mechanisms, as they enable capturing the dynamic nature of disease‐related alterations. By means of parallel profiling using a multi‐omics approach, we aim to disentangle the complex nature of schizophrenia's aetiology. Here, we will outline how this system‐based analysis approach can contribute to the discovery of disease mechanisms in schizophrenia and in turn other psychiatric disorders.

British Journal of Pharmacology (2008) 153, S133–S136; doi:10.1038/sj.bjp.0707658; published online 14 January 2008