bluuebunny/crossref_metadata_2025 huggingface dataset:
Horizontal rhythmical eye movements consistently diminish the arousal provoked by auditory stimuli
Authors: Barrowcliff Alastair L. , Gray Nicola S. , MacCulloch Sophie , Freeman Tom C. A. , MacCulloch Malcolm J.
Published: September 2003

Objectives:Theoretical models implicating the orienting reflex as an explanatory mechanism in the eye‐movement desensitization and reprocessing (EMDR) treatment protocol are contrasted and tested empirically. We also test whether EMDR effects are due to a distraction effect.

Design:A repeated measure design is used in two experiments. The first experiment employed two independent variables, eye condition (moving vs. stationary) and tone (a pseudo‐randomized series of low and high intensity tones). In Expt 2, eye condition was replaced by attentional demand conditions (low or high). In both cases, electrodermal responses served as the dependent variable.

Method:Participants were recruited from the Psychology Department at Cardiff University. In Expt 1, participants were required to either pursue a moving stimulus following auditory challenge or engage in an eyes‐stationary task. In Expt 2, the task following auditory challenge required participants to identify specific items from letter strings in low and high attentional demand conditions.

Results:Lower levels of electrodermal arousal were identified in tasks eliciting eye movements, compared to no eye movements. This effect was not due to the attentional requirements of the task.

Conclusions:Eye movements following auditory challenge result in an effect of psychophysiological de‐arousal. This supports the reassurance reflex model of EMDR proposed by MacCulloch and Feldman (1996).
How robust is performance on the National Adult Reading Test following traumatic brain injury?
Authors: Riley Gerard A. , Simmonds Lincoln V.
Published: September 2003

Objective:To investigate whether National Adult Reading Test (NART) performance may be impaired by severe traumatic brain injury (TBI).

Method:A sample of 26 people who had been given a NART within 12 months of a severe TBI was given a second NART at least 12 months after the first NART.

Results:Mean performance on the second NART was significantly better than performance on the first NART. Of the participants, 11 (42%) showed an improvement of more than 5 IQ points in respect of the verbal IQ estimates based on their NART scores, with three participants showing an improvement of 20 points. In applying the NART to determine the presence of an acquired intellectual impairment, use of the first NART scores alone would have resulted in such impairments being missed in at least 25% of a subsample of 16 participants for whom an actual verbal IQ had been obtained at the time of the first NART.

Conclusion:An NART given within 12 months of a severe TBI runs the risk of significantly underestimating pre‐morbid IQ. If applied in this context, it is recommended that the NART score is used in conjunction with other methods of estimation, such as those based on demographic data.
Factors predicting long‐term survival in low‐risk diffuse large B‐cell lymphoma
Authors: Møller Michael B. , Pedersen Niels T. , Christensen Bjarne E.
Published: September 2003

The International Prognostic Index (IPI) is widely used for risk stratification of patients with diffuse large B‐cell lymphoma (DLBCL). However, even among patients with low‐risk disease, according to the IPI a substantial proportion of patients ultimately succumb to their disease. Using mature population‐based data from the Danish Lymphoma Group, we analyzed if prognostic clinical pretreatment factors could be identified in patients with low‐risk DLBCL. One hundred seventy‐seven patients, all with a prognostic profile as favorable as possible according to the IPI and treated with anthracycline‐based combination chemotherapy (92%) or loco‐regional radiotherapy/surgery (8%) with curative intent were included. The median age was 50 years and 170 achieved complete remission. The median follow‐up time was 11 years. Twenty‐six patients relapsed, with a median time to relapse of 12.1 months. Overall survival at 5 years and 10 years was 85% and 75%, respectively. Stage II was associated with poor response to treatment (P = 0.044). In a multivariate analysis, Stage II (P = 0.001) and age >50 years (P = 0.043) were independently associated with poor outcome. Patients without these adverse factors had an excellent prognosis, with a survival at 5 and 15 years of 90% and 80%, respectively. In contrast, patients with both adverse factors had poor outcome, with survival at 5 and 15 years of 70% and 29%, respectively (P < 0.001). The present data suggest that risk stratification of DLBCL patients with a favorable IPI score can be improved by the simple use of two clinical pretreatment factors. Am. J. Hematol. 74:94–98, 2003. © 2003 Wiley‐Liss, Inc.
Two factor XI mutations in a Chinese family with factor XI deficiency
Authors: Au W.Y. , Cheung J.W. , Lam C.C.K. , Kwong Y.L.
Published: September 2003

We describe a Chinese family with factor XI deficiency, the first reported to date. The proband had factor XI activity of 1% and was heterozygous for two nonsense mutations, an exon‐8 C713→T mutation resulting in Gln263→Term, and an exon‐10 C979→A mutation resulting in Tyr351→Term. Two daughters were heterozygous for the Gln263→Term mutation and two for the Try351→Term mutation. All showed a reduction of factor XI activity to about 50%. The Gln263→Term mutation has been described in two Japanese families, and it remains to be determined whether a common founder exists between the three kindreds. The Try351→Term mutation is novel. Am. J. Hematol. 74:136–138, 2003. © 2003 Wiley‐Liss Inc.
High‐resolution methylation analysis of the hMLH1 promoter in sporadic endometrial and colorectal carcinomas
Authors: Strazzullo Maria , Cossu Antonio , Baldinu Paola , Colombino Maria , Satta Maria P. , Tanda Francesco , De Bonis Maria L. , Cerase Andrea , D'Urso Michele , D'Esposito Maurizio , Palmieri Giuseppe
Published: September 2003

BACKGROUND

Microsatellite instability (MSI) has been reported in endometrial carcinoma (EC) and in colorectal carcinoma (CRC), primarily as a result of defective DNA mismatch repair (MMR). The MMR gene hMLH1 commonly is inactivated in both EC and CRC. In the current study, epigenetic mechanisms involved in hMLH1 inactivation have been investigated to further elucidate the role of these mechanisms in the pathogenesis of EC and CRC.

METHODS

Polymerase chain reaction (PCR)‐based microsatellite analysis performed on paraffin‐embedded tissues was used to select 42 sporadic carcinomas (21 ECs and 21 CRCs) with MSI. Immunohistochemistry (IHC), using the anti‐hMLH1 antibody, and mutation analysis, using denaturing high‐performance liquid chromatography and automated sequencing, were performed on unstable carcinoma samples. Methylation analysis, using modified protocols for bisulfite treatment and methylation‐specific PCR (MSP), was performed on DNA from archival tissue samples.

RESULTS

No MSI‐positive tumor samples with normal hMLH1 immunostaining (n = 7) exhibited hMLH1 promoter methylation, whereas 8 of 35 unstable cases with loss of hMLH1 expression (23%) exhibited MSP amplification. Among analyzed cases, germ‐line mutations of hMLH1 were found in 4 of 20 unmethylated samples (20%) and in 0 of 8 methylated samples. Bisulfite sequencing of amplification products from methylated samples demonstrated that almost all CpG dinucleotides within the hMLH1 promoter elements underwent methylation.

CONCLUSIONS

Although an MMR gene other than hMLH1 may be responsible for genetic instability in MSI‐positive/IHC‐positive tumors, the presence of MSP amplification and allelic deletions within the hMLH1 locus in subsets of MSI‐positive/IHC‐negative cases strongly suggests that hMLH1 promoter methylation may contribute to the inactivation of both hMLH1 alleles. Bisulfite analysis suggests that the mechanisms of hMLH1 silencing may depend on CpG density rather than site‐specific methylation. Cancer 2003;98:1540–6. © 2003 American Cancer Society.

DOI 10.1002/cncr.11651
Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy
Authors: Becker Karen , Mueller James D. , Schulmacher Christoph , Ott Katja , Fink Ulrich , Busch Raymonde , Böttcher Knut , Siewert J. Rüdiger , Höfler Heinz
Published: September 2003

BACKGROUND

Neoadjuvant chemotherapy has shown some success in the treatment of gastric carcinoma, but objective parameters for measuring its effects are lacking. The authors performed the current study to determine which histomorphologic features are correlated with patient prognosis after chemotherapy.

METHODS

Thirty‐six patients with gastric carcinoma were treated with a combination of etoposide, doxorubicin, and cisplatin. The entire tumor beds of the specimens were evaluated histologically and compared with specimens treated with surgery alone. Thirty‐four patients were available for survival analysis (follow‐up period, 60–130 months).

RESULTS

None of the 36 patients had complete tumor regression, 4 patients had marked regression (less than 10% viable tumor), 9 patients had regression to 10–50% remaining viable tumor, and 23 patients had more than 50% viable tumor remaining. Currently, 9 patients are still alive (5‐year survival rate, 27%). Tumor regression was found to be correlated significantly with survival (P = 0.01), but tumor size (P = 0.002) and lymphatic vessel invasion (P = 0.003) were better predictors of prognosis.

CONCLUSIONS

Histologic tumor regression grade is an objective measure of the effects of neoadjuvant chemotherapy in patients with gastric carcinoma, but its accuracy may be improved by adding additional staging variables such as tumor size and lymphatic vessel involvement. Cancer 2003;98:1521–30. © 2003 American Cancer Society.

DOI 10.1002/cncr.11660
Effect of education level on outcome of patients treated on Radiation Therapy Oncology Group Protocol 90‐03
Authors: Konski Andre , Berkey Brian A. , Kian Ang K. , Fu Karen K.
Published: September 2003

BACKGROUND

It has been hypothesized that people in lower socioeconomic groups have worse outcomes because they present with advanced‐stage cancers or receive inadequate treatment. The authors investigated this hypothesis by using education level as a proxy for socioeconomic status in patients treated on Radiation Therapy Oncology Group (RTOG) Protocol 90‐03.

METHODS

RTOG 90‐03 was a Phase III randomized trial investigating four different radiation fractionation schedules in the treatment of locally advanced head and neck carcinomas. Overall survival and locoregional control rates were analyzed by education level as measured by patient response on the demographic form at study entry.

RESULTS

A significant difference was observed in the distribution of patients by education level between the standard fractionated radiation treatment arm and the hyperfractionated radiation treatment arm. More patients in the standard fractionated treatment arm had a higher education level (P= 0.018). Patients attending college had highly and significantly better overall survival and locoregional control than the other groups combined (P= 0.0056 andP= 0.025, respectively: from Cox proportional hazards models stratified by assigned treatment with educational level, T classification, N classification, Karnofsky performance status, primary site, and race). Multivariate analysis revealed that education level was significant for predicting both overall survival and locoregional control when comparing attended college/technical school compared with all other education levels.

CONCLUSIONS

Patients attending college or technical school had improved overall survival and locoregional control. These differences cannot be explained by differences in tumor stage or treatment. Poorer overall health or lack of support systems contributing to these results needs to be investigated further. Cancer 2003;98:1497–503. © 2003 American Cancer Society.

DOI 10.1002/cncr.11661
The biology and therapy of adult acute lymphoblastic leukemia
Authors: Faderl Stefan , Jeha Sima , Kantarjian Hagop M.
Published: September 2003

BACKGROUND

Much progress has been made in understanding the biology of acute lymphoblastic leukemia (ALL). This has translated into the recognition of several subgroups of ALL and the institution of risk‐adapted therapies. New therapies are emerging based on the definition of specific cytogenetic‐molecular abnormalities.

METHODS

A review from the English literature, including original articles and related reviews from Medline (Pubmed) and abstracts based on publication of meeting material, was performed.

RESULTS

Changes in the pathologic classification of ALL have led to therapeutic consequences. Adaptation of successful treatment strategies in children with ALL has resulted in similar complete response rates in adults. Prognosis has especially improved in mature–B‐cell and T‐lineage ALL. The role of tyrosine kinase inhibitors in Philadelphia chromosome–positive ALL was evaluated in the current study. However, regardless of the ALL subgroup, long‐term survival of adults is still inferior to that in children.

CONCLUSIONS

Intense clinical and laboratory research is attempting to close the gap in outcome between children and adults with ALL. Investigations are focusing on 1) refinement of the basic treatment stratagem of induction, consolidation, and maintenance; 2) expansion of risk‐based, subgroup‐oriented therapies; 3) assessment of minimal residual disease, its impact on disease recurrence, and its practical implications in clinical practice; 4) salvage strategies; 5) the role of stem cell transplantation in ALL; and 6) the development of new drugs based on a better understanding of disease biology. Cancer 2003;98:1337–54. © 2003 American Cancer Society.
Alternative decision modelling techniques for the evaluation of health care technologies: Markov processes versus discrete event simulation
Authors: Karnon Jonathan
Published: September 2003

Markov models have traditionally been used to evaluate the cost‐effectiveness of competing health care technologies that require the description of patient pathways over extended time horizons. Discrete event simulation (DES) is a more flexible, but more complicated decision modelling technique, that can also be used to model extended time horizons. Through the application of a Markov process and a DES model to an economic evaluation comparing alternative adjuvant therapies for early breast cancer, this paper compares the respective processes and outputs of these alternative modelling techniques. DES displays increased flexibility in two broad areas, though the outputs from the two modelling techniques were similar. These results indicate that the use of DES may be beneficial only when the available data demonstrates particular characteristics. Copyright © 2002 John Wiley & Sons, Ltd.
Conservative versus aggressive follow up of mildly abnormal Pap smears: Testing for process utility
Authors: Birch Stephen , Melnikow Joy , Kuppermann Miriam
Published: September 2003

Economic evaluation generally limits outcome measurement to the valuation of health outcomes produced by interventions without considering the impact of processes on utility. We test for process utility by comparing utility measurements for alternative approaches to managing abnormal Pap smears in the context of a fixed outcome. The impact of health care interventions on individual well‐being was not confined to health outcomes. Aggressive and conservative follow‐up approaches were associated with statistically significant differences in utilities. We also found that relative preferences among different processes may depend on the particular circumstances or pathologies being considered. Copyright © 2003 John Wiley & Sons, Ltd.
Reflections on the optimal currency area (OCA) criteria in the light of EMU
Authors: Artis M.J.
Published: September 2003

Optimal Currency Area (OCA) theory offers criteria for evaluating the optimality of monetary union arrangements. This paper reviews the use that has been made of these criteria in the specific context of European Monetary Union. It reviews the use of business cycle synchronization data and the data produced by SVAR analyses, which led to the ‘core–periphery’ distinction. It also reviews extensions of the criteria that have been proposed or generated in this context: in particular, the proposition that the criteria may be ‘endogenous’. It presents Taylor rule estimates to check for inhomogeneities in Euro Area performance. The paper concludes that OCA criteria provide a useful starting point for evaluating monetary union options. Copyright © 2003 John Wiley & Sons, Ltd.
The federal design of a central bank in a monetary union: The case of the European system of central banks
Authors: Eijffinger Sylvester C.W.
Published: September 2003

In this paper we analyse the ESCB as a federal central bank system. First, the degree of decentralization of the ESCB will be briefly compared with its predecessor, the Deutsche Bundesbank, and its counterweight in the US, the Federal Reserve System. Moreover, the development during the period 1990–99 of the total, economics and research staffing of the ECB and the national central banks in the EU will be investigated and also the staff ratios of the national central banks in 1999. Furthermore, the research activities of the central banks in the European Union over the period 1990–99 will be analysed both in terms of input (economics and research staff) and output (quality‐weighted number of articles in scientific journals). The share of economics research staff in total staff of the national central banks varies between 0.02 and 0.17. The ECB has the highest ratio between economists and researchers and other staff. A ranking of research performance based on the quality‐weighted number of scientific articles per economics and research employee reveals that the Bank of Finland has the best research performance of European central banks, followed by De Nederlandsche Bank, the Banco de Portugal and the Oesterreichische Nationalbank. There is only a weak relationship between the research performance and the share of research staff. The conclusion ‘small is beautiful’ also seems to hold for the economics and research departments of the European central banks. Copyright © 2003 John Wiley & Sons, Ltd.
Dollarization and economic performance: What do we really know?
Authors: Edwards Sebastian , Magendzo I. Igal
Published: September 2003

In this paper we analyse the macroeconomic record of dollarized economies. In particular, we investigate whether, as its supporters claim, dollarization is associated with lower inflation and faster growth. We analyse this issue by using a matching estimator technique developed in the training evaluation literature. Our findings suggest that inflation has been significantly lower in dollarized nations than in non‐dollarized ones. We also find that dollarized nations have had a lower rate of economic growth than non‐dollarized ones. Finally, we find that macroeconomic volatility is not significantly different across dollarized and non‐dollarized economies. We conjecture that the lower rate of economic growth in dollarized countries is due, at least in part, to these countries' difficulties in accommodating external disturbances, such as major terms of trade and capital flows shocks. Copyright © 2003 John Wiley & Sons, Ltd.
DNA‐binding characteristics of cnidarian Pax‐C and Pax‐B proteins in vivo and in vitro: No simple relationship with the Pax‐6 and Pax‐2/5/8 classes
Authors: Plaza Serge , De Jong Danielle M. , Gehring Walter J. , Miller David J.
Published: September 2003

Cnidarians are the simplest animals in which distinct eyes are present. We have previously suggested that cnidarian Pax‐Cam might represent a precursor of the Pax‐6 class. Here we show that when expressed in Drosophila imaginal discs, Pax‐Cam chimeric proteins containing the C‐terminal region of EY were capable of eye induction and driving expression of a reporter gene under the control of a known EY target (the sine oculis gene). Whilst these results are consistent with a Pax‐6‐like function for Pax‐Cam, in band shift experiments we were unable to distinguish the DNA‐binding behaviour of the Pax‐Cam Paired domain from that of a second Acropora Pax protein, Pax‐Bam. The ability of a Pax‐Bam/EY chimera to also induce eye formation in leg imaginal discs, together with the in vitro data, cast doubt on previously assumed direct relationships between cnidarian Pax genes and the Pax‐6 and Pax‐2/5/8 classes of bilateral animals. J. Exp. Zool. (Mol. Dev. Evol.) 299B:26–35, 2003. © 2003 Wiley‐Liss, Inc.
Breath‐hold signal‐loss sequence for the qualitative assessment of flow disturbances in cardiovascular MR
Authors: Keegan Jennifer , Gatehouse Peter D. , John Anna S. , Mohiaddin Raad H. , Firmin David N.
Published: September 2003

Purpose

To develop a breath‐hold segmented sequence which generates similar patterns of signal loss to a non–breath‐hold, relatively long echo time, conventional gradient echo sequence for the qualitative assessment of valvular heart disease.

Materials and Methods

Both velocity‐sensitized and acceleration‐sensitized segmented sequences were developed. The sensitivities were empirically adjusted to give similar degrees of signal loss to a conventional sequence. These sequences were compared with a conventional sequence in eight patients with flow disturbances and in four healthy subjects.

Results

There was no significant difference in the extent of signal loss observed when using the breath‐hold velocity‐ and acceleration‐sensitized sequences developed and the conventional sequence (1862 mm2, 1831 mm2, and 1782 mm2, respectively; P = ns). However, the image quality obtained was significantly better with the breath‐hold sequences (both P < 0.01). Furthermore, the image quality achieved with the acceleration‐sensitized sequence was significantly better than that achieved with the velocity‐sensitized sequence (P < 0.01) where artifacts from beat‐to‐beat variations in blood‐flow velocities were a frequent problem.

Conclusion

Signal loss in complex flow is best demonstrated using the breath‐hold acceleration‐sensitized sequence where the signal from both stationary and constant velocity material is rephased at the echo time.
Soil restorative effects of mulching on aggregation and carbon sequestration in a Miamian soil in central Ohio
Authors: Saroa G. S. , Lal R.
Published: September 2003

Soils play a key role in the global carbon cycle, and can be a source or a sink of atmospheric carbon (C). Thus, the effect of land use and management on soil C dynamics needs to be quantified. This study was conducted to assess: (1) the role of aggregation in enhancing soil organic carbon (SOC) and total soil nitrogen (TSN) concentrations for different mulch rates, (2) the association of SOC and TSN with different particle size fractions, and (3) the temporal changes in the SOC concentration within aggregate and particle size fractions with duration of mulching. Two experiments were initiated, one each in 1989 and 1996, on a Crosby silt loam (Aeric Ochraqualf or Stagnic Luvisol) in central Ohio. Mulch treatments were 0, 8, and 16 Mg ha−1 yr−1 without crop cultivation. Soil samples from 0–5 cm and 5–10 cm depths were obtained in November 2000; 4 and 11 years after initiating the experiments. Mulch rate significantly increased SOC and TSN concentrations in the 0–5 cm soil layer only. The variation in the SOC concentration attributed to the mulch rate was 41 per cent after 4 years of mulching and 52 per cent after 11 years of mulching. There were also differences in SOC and TSN concentrations among large aggregate size fractions, up to 2 mm size after 4 years and up to 0ċ5 mm after 11 years of mulching. There were also differences in SOC and TSN concentrations among particle size fractions. Variation in the SOC concentration in relation to particle size was attributed to clay by 45–51 per cent, silt by 34–36 per cent, and to sand fraction by 15–19 per cent. Bulk of the TSN (62–67 per cent) was associated with clay fraction and the rest was equally distributed between silt and sand fractions. The enrichment of SOC and TSN concentrations in the clay fraction increased with depth. The C:N ratio was not affected by the mulch rate, but differed significantly among particle size fractions; being in the order of sand >silt >clay. Copyright © 2003 John Wiley & Sons, Ltd.
Surgery for early stage non‐small cell lung cancer
Authors: Chang Michael Y. , Sugarbaker David J.
Published: September 2003

Lung cancer accounts for 28.2% of all cancer‐related deaths in the United States. Most patients present with advanced‐stage disease, with only 15% having disease confined to the lung. Surgical resection is the optimal treatment for Stage I and II non‐small cell lung cancer. Pre‐resection staging includes various radiographic modalities, including PET scan and mediastinoscopy. Survival and local recurrence statistics favor full anatomic lobar resection over sublobar resection, although cases must be judged individually. Lobectomy via thoracoscopic approach appears to have equivalent outcome as lobectomy via thoracotomy. Characteristics of the counseling physician and the hospital volume at which the surgery is performed can also influence outcome. After surgical resection, stage IA patients have about 70% 5‐year survival, but this falls below 50% for stage IIB patients. Methods that identify early‐stage lung cancer patients at greatest risk for recurrence are needed to identify patients who may benefit from additional therapies. Semin. Surg. Oncol. 21:74–84, 2003. © 2003 Wiley‐Liss, Inc.
Surgery for locally advanced non‐small cell lung cancer
Authors: Grunenwald Dominique H.
Published: September 2003

Advanced stage non‐small lung cancers are currently considered unresectable. However numerous series on patients with locally advanced disease treated by surgery have been published. Surgery alone or induction treatments followed by surgery achieve long‐term outcomes in an encouraging proportion of selected patients with T4 disease, despite the high rate of morbidity associated with technically demanding procedures. Semin. Surg. Oncol. 21:85–90, 2003. © 2003 Wiley‐Liss, Inc.
Induction chemotherapy followed by radical local therapy for locally advanced non‐small cell lung cancer
Authors: Wendland Merideth M. M. , Sause William T.
Published: September 2003

Many patients who receive a diagnosis of non‐small cell lung cancer (NSCLC) have locally advanced disease at initial presentation. Historically, these patients were treated with primary thoracic radiation therapy and had poor long‐term survival rates, secondary to both progression of local disease and development of distant metastases. With the goal of improving clinical outcomes, multiple concepts of combined‐modality therapy for locally advanced NSCLC have been investigated. The rationale for using chemotherapy in the induction regimen is to eliminate subclinical metastatic disease while improving local control. The optimal treatment of locally advanced NSCLC continues to evolve, but combined‐modality therapy has led to improved survival rates compared to treatment with radiation alone and has become the new standard of care. This report reviews the major trials that have investigated various combinations of surgery, radiation therapy, and chemotherapy in the treatment of locally advanced NSCLC. Semin. Surg. Oncol. 21:111–121, 2003. © 2003 Wiley‐Liss, Inc.
Limited‐disease small‐cell lung cancer
Authors: Zimmermann Frank B. , Bamberg Michael , Molls Michael , Jeremic Branislav
Published: September 2003

Substantial improvements in treatment outcome for limited‐disease small‐cell lung cancer (LD SCLC) have been achieved in the last two decades owing to the introduction of chemotherapy (CHT) consisting of cisplatin and etoposide (PE), and the understanding that thoracic radiation therapy (TRT) is an essential component in improving treatment outcome. In addition, a recent metaanalysis confirmed the importance of prophylactic cranial irradiation (PCI) in general treatment plans for patients who show a complete response to treatment. However, numerous questions remain unanswered regarding this disease. While TRT/PE/PCI is considered to be the standard treatment in the majority of centers worldwide, the emergence of new and effective drugs (e.g., topoisomerase I inhibitors and paclitaxel) for the treatment of LD SCLC will likely affect therapy strategies in the near future. Important issues regarding optimal doses and fractionation regimens, as well as the timing of TRT, remain to be resolved. While most centers currently use b.i.d. fractionation as a result of the Intergroup findings, high‐dose standard TRT may also be beneficial. TRT volumes are also considered an important issue, since they likely relate to the incidence of both local failure and toxicity. Finally, the optimization of PCI (total dose, fractionation regimen, and timing) is already under way. The value of surgery is limited to peripheral tumors and poorly responding cancer, and to confirm histology or improve local control and survival. Semin. Surg. Oncol. 21:156–163, 2003. © 2003 Wiley‐Liss, Inc.
Extensive‐stage small‐cell lung cancer
Authors: Spira Alexander , Ettinger David S.
Published: September 2003

Extensive‐stage small‐cell lung cancer (ES‐SCLC) continues to be a difficult management issue. While response rates to therapy are relatively high, durable responses are rare, and long‐term survival rates are dismal. Although many attempts have been made to develop new therapies, cisplatin‐based combination chemotherapy remains the mainstay in the management of these patients. In this review we highlight recent developments in the treatment and management of this malignancy, and discuss future prospects in treatment. Semin. Surg. Oncol. 21:164–175, 2003. © 2003 Wiley‐Liss, Inc.
Curative approaches to lung cancer in the elderly
Authors: Weinmann Martin , Zimmermann Frank , Bamberg Michael , Jeremic Branislav
Published: September 2003

Lung cancer is a common disease in elderly patients, and the increase in the size of the elderly population will lead to an increased proportion of elderly among lung cancer patients in the future. The prognosis of lung cancer is still poor, but curative approaches are feasible for patients with local stage NSCLC and for some patients with limited disease (LD) SCLC. The evidence for these curatively‐intended approaches is derived from studies that are usually performed with highly selected patients. Elderly patients are underrepresented, and in daily clinical practice elderly patients are less likely to be treated with full standard approaches. We used the data from studies that focused particularly on the elderly, or provided subgroup information on age, to analyze the feasibility of applying current standard approaches to the elderly. We also discuss alternative approaches. Age alone is a very uncertain prognostic criterion for outcome or tolerability of treatment. It is much more important to obtain a comprehensive geriatric assessment of each individual patient. When adequate patient selection is provided, standard treatment approaches appear to be feasible for elderly (>70 years) patients with good performance status. Semin. Surg. Oncol. 21:182–189, 2003. © 2003 Wiley‐Liss, Inc.
New radiotherapy technologies
Authors: Rosenzweig Kenneth E. , Amols Howard , Ling C.C.
Published: September 2003

Conventional radiation therapy has had limited success in curing inoperable lung cancer due to poor local control. There is evidence to suggest that higher doses of radiation will improve local control. In order to safely deliver higher doses of thoracic radiation, advanced treatment techniques are required. Different biologic indices have been utilized to determine whether dose escalation can be safely accomplished, and the results have been reported from many institutions. Tumor motion control aids in treatment since it allows radiation oncologists to more accurately target tumors and therefore to spare more normal tissue from the radiation field. The imaging information from 18‐FDG‐PET scans also improves target delineation. Advanced treatment delivery techniques, such as three‐dimensional conformal radiation therapy, intensity modulated radiation therapy, and stereotactic radiosurgery are also being used to safely escalate the radiation dose. This article explores the current literature on these issues and other advanced radiation therapy techniques. Semin. Surg. Oncol. 21:190–195, 2003. © 2003 Wiley‐Liss, Inc.
Impaired disengagement from threatening cues of impending pain in a crossmodal cueing paradigm
Authors: Van Damme Stefaan , Crombez Geert , Eccleston Chris , Goubert Liesbet
Published: September 2003

This paper reports an experimental investigation of attentional engagement to and disengagement from cues of impending pain. Pain‐free volunteers performed a cueing task in which they were instructed to detect somatosensory and tone targets. Target stimuli were preceded by visual cues informing participants of the modality of the impending stimuli. Participants were randomly assigned to a pain group (n=54) or to a control group (n=53). Somatosensory targets consisted of painful electrocutaneous stimuli in the pain group and non‐painful vibrotactile targets in the control group. Analyses revealed a similar amount of attentional engagement to both cues signalling somatosensory targets, irrespective of their threat value. However, participants had significantly more difficulty in disengaging attention from a threatening cue of impending pain compared to a cue signalling the non‐painful vibrotactile target. Our findings provide further evidence that pain cues demand attention, particularly resulting in impaired disengagement.
Control of mitochondrial protein import by pH
Authors: Grigoriev Sergey M , Jensen Robert E , Kinnally Kathleen W
Published: September 2003

Protein import into mitochondria is inhibited by protons (IC50 pH 6.5). The channels of the import machinery were examined to further investigate this pH dependence. TOM and TIM23 are the protein translocation channels of the mitochondrial outer and inner membranes, respectively, and their single channel behaviors at various pHs were determined using patch‐clamp techniques. While not identical, increasing H+ concentration decreases the open probability of both TIM23 and TOM channels. The pattern of the pH dependences of protein import and channel properties suggests TIM23 open probability can limit import of nuclear‐encoded proteins into the matrix of yeast mitochondria.
Sodium channel modulating activity in a δ‐conotoxin from an Indian marine snail
Authors: Sudarslal S , Majumdar Sriparna , Ramasamy P , Dhawan Ritu , Pal Prajna P , Ramaswami Mani , Lala Anil K , Sikdar S.K , Sarma Siddhartha P , Krishnan K.S , Balaram P
Published: September 2003

A 26 residue peptide (Am 2766) with the sequence CKQAGESCDIFSQNCCVG‐TCAFICIE‐NH2 has been isolated and purified from the venom of the molluscivorous snail, Conus amadis, collected off the southeastern coast of India. Chemical modification and mass spectrometric studies establish that Am 2766 has three disulfide bridges. C‐terminal amidation has been demonstrated by mass measurements on the C‐terminal fragments obtained by proteolysis. Sequence alignments establish that Am 2766 belongs to the δ‐conotoxin family. Am 2766 inhibits the decay of the sodium current in brain rNav1.2a voltage‐gated Na+ channel, stably expressed in Chinese hamster ovary cells. Unlike δ‐conotoxins have previously been isolated from molluscivorous snails, Am 2766 inhibits inactivation of mammalian sodium channels.
pkn22 (alr2502) encoding a putative Ser/Thr kinase in the cyanobacterium Anabaena sp. PCC 7120 is induced by both iron starvation and oxidative stress and regulates the expression of isiA
Authors: Xu Wen-Liang , Jeanjean Robert , Liu Yong-Ding , Zhang Cheng-Cai
Published: September 2003

In cyanobacteria, the isiA gene is required for cell adaptation to oxidative damage caused by the absence of iron. We show here that a putative Ser/Thr kinase gene, pkn22 (alr2052), is activated by iron deficiency and oxidative damage in Anabaena sp. PCC 7120. A pkn22 insertion mutant is unable to grow when iron is limiting. pkn22 regulates the expression of isiA (encoding CP43′), but not of isiB (encoding flavodoxin) and psbC (CP43). Fluorescence measurement at 77 K reveals the absence of the typical signature of CP43′ associated with photosystem I in the mutant under iron‐limiting conditions. We propose that Pkn22 is required for the function of isiA/CP43′ and constitutes a regulatory element necessary for stress response.
Coordination problem and grand coalition: the puzzle of the government formation game in the Czech Republic, 1998☆
Authors: Nikolenyi Csaba
Published: September 2003

After the 1998 general elections to the Chamber of Deputies of the Czech Republic, the largest party, the Social Democrats, formed a minority government. The formation of this government was puzzling for at least four reasons. First, according to the so-called Opposition Pact, the minority government was supported from the outside by the conservative Civic Democratic Party, the principal opponent of the Social Democrats in the party system. Second, the grand legislative coalition was not followed by the sharing of executive portfolios between the two largest parties. Third, the two parties entered into this agreement only weeks after they had explicitly stated their unwillingness to govern together. Fourth, neither theories of coalition formation nor those of minority government formation provide an accurate prediction for this outcome. This article provides a solution for these puzzles based on a game theoretic analysis.
The characterization of sardine (Sardina pilchardus Walbaum) schools off the Spanish-Atlantic coast
Authors: Muiño Ramón , Carrera Pablo , Iglesias Magdalena
Published: September 2003

This paper describes the main characteristics of sardine schools detected in the Spanish-Atlantic surveys carried out from 1992 to 1997 (except 1994). A series of parameters were obtained for each school (morphological, positional and energetic) as well as environmental factors (temperature and salinity). The relationships between the school parameters were analyzed by a PCA and then the school parameters per se were described using both univariate and multivariate analyses (Box-plots, ANOVAs, MANOVA, and discriminant analysis). The results show that significant differences exist between years and geographic areas in that the Rías Baixas schools were smaller in size and of higher density than those from the Cantabric area. These differences could be related to the facts that the Rías Baixas is a nursery zone and sardine length and age are smaller than in the Cantabric Sea. It would seem that the differences in school morphology and energetic characteristics related to length and age of individuals allow us to distinguish between the sardine echo traces in this area. There is a high annual variability in the number of schools and this is not a function of either survey design or strategy and it is not related to the abundance estimates of sardine. These results are important for both future species identification and the improvement of survey design and strategy.
THE POLITICAL CULTURE OF THE SCOTTISH HIGHLANDS FROM CULLODEN TO WATERLOO
Authors: MACKILLOP ANDREW
Published: September 2003

This article highlights the present lacuna in the study of politics and political culture in the Scottish Highlands between the battles of Culloden and Waterloo. It argues that this neglect is symptomatic of the contentious historiography that surrounds the Highland Clearances. Yet politics remained a crucial factor shaping landlord attitudes to improvements and their estates in general. Moreover, in contrast to their well-known failure to manage the region's economic and social development, Highland landlords exhibited a sophisticated understanding of how British politics had been reconfigured by the emergence of the British ‘fiscal-military’ state. The region's elites constructed a distinctive and effective political strategy that sought to place the Highlands in a mutually supportive relationship with the British state. Scottish Highland political culture thus offers a useful corrective to recent debates on the ‘fiscal-military’ state that stress either the centre's overwhelming power or the ability of local elites to resist that power. Although the Highlands is remembered primarily for its hostile relationship with the political centre, the region in fact constituted a prime example of the process of mutual accommodation that underpinned the domestic authority of the eighteenth-century British state.
CARE OR CONTROL? THE METROPOLITAN WOMEN POLICE AND CHILD WELFARE, 1919–1969
Authors: JACKSON LOUISE A.
Published: September 2003

The term ‘policing’ is often used to refer to a broad range of regulatory practices, which have been associated with the development of educative and social work frameworks in the modern state. The relationship between the concepts of ‘welfare’ and ‘penality’ (or ‘care’ and ‘control’) has been the subject of a number of recent studies of social intervention in twentieth-century Britain. However, the role of police officers themselves in the ‘policing of families’ has rarely been elaborated. From their initial appointment to London's Metropolitan Police in 1919 until their official integration on the same terms as male officers in the early 1970s, women police officers played a significant role in the detection and prevention of child abuse, neglect, and female delinquency. Through a case study of the work of the Metropolitan Women Police branch, this article considers the negotiation of a social work ethic within policing as well as the shifting configuration of the ‘care’/‘control’ nexus in welfare legislation and professional practice. The Metropolitan Women Police tended to see ‘care’ and ‘control’ as mutually reinforcing rather than conflicting concepts. Such a formulation was resonant with the rhetoric of social work and official legislation until the early 1960s. It also reflected the philosophy of crime prevention laid down as the principal object of policing, enabling women to justify involvement in child protection and welfare as an aspect of police work.
Variation in the free amino acid concentrations of the supralittoral rockpool copepod crustacean Tigriopus brevicornis during osmotic stress
Authors: McAllen Rob
Published: September 2003

Changes in the intracellular free amino acid (FAA) concentrations of Tigriopus brevicornis when subjected to hypoosmotic (5 psu), normal seawater (35 psu) and hyperosmotic (70 psu) conditions for a three day acclimation period were investigated. Proline, alanine and lysine were the major contributors to the intracellular FAA pool. Under hypoosmotic conditions, alanine was the dominant osmolyte with proline concentration at its lowest. This trend was reversed under hyperosmotic conditions. However, the total FAA pool was at its highest concentration under normal seawater conditions, with the total FAA concentrations being reduced during hypo- and hyper-osmotic conditions.
Reproduction in the amphipod, Echinogammarus marinus: a comparison between normal and intersex specimens
Authors: Ford Alex T. , Fernandes Teresa F. , Rider Sebastien A. , Read Paul A. , Robinson Craig D. , Davies Ian M.
Published: September 2003

The fecundity and occurrence of intersexuality in the amphipod, Echinogammarus marinus, collected from populations on the east coast of Scotland are reported. Intersex specimens have significantly smaller mean brood sizes than normal specimens. Embryo survival, as measured by the ratio of eggs/embryos in early and late stages of development, is lower in intersex specimens than normal specimens. Greater differences in the number of early stage eggs compared with late stage eggs in intersex specimens is suggested to arise by the active ejection of non-viable eggs, or from the passive loss of eggs through malformed brood plates in females. An apparent reduction in brood sizes between early and late stages of development in ‘normal’ specimens, emphasizes the importance of quantifying different egg/embryo stages in amphipod toxicology and fecundity studies.
Timing of sex disturbance caused by tributyltin exposure during the embryonic stage in the caprellid amphipod, Caprella danilevskii
Authors: Ohji Madoka , Arai Takaomi , Miyazaki Nobuyuki
Published: September 2003

Caprellid amphipods, Caprella danilevskii were exposed to tributyltin (TBT) (100 ng 1−1) for ten periods after eggs were deposited in the brood pouch. Brood loss during incubation was found in six exposure periods between 12 and 72 h after spawning, although no brood loss was observed in the control. It was suggested that exposure to TBT half a day after spawning might be sufficient to damage reproduction during the caprellid's embryonic life. The female percentage was 38.7% in the control, whereas it was gradually increased to 60.0–71.4% in the four exposure periods between 12 and 48 h after spawning.
Do the age compositions and growth of the crab Portunus pelagicus in marine embayments and estuaries differ?
Authors: de Lestang S. , Hall N.G. , Potter I.C.
Published: September 2003

Portunus pelagicus (Crustacea: Portunidae) was collected monthly for a minimum of two years from two marine embayments (Cockburn Sound and Koombana Bay) and two estuaries (Peel-Harvey and Leschenault) that are located between 32° and 33°S on the lower west coast of Australia. A birth date of 1 December, derived from estimates of the peak time of spawning, was used to determine the average age of crabs in the main size cohort(s) in carapace width–frequency histograms for each month in each water body. The resultant carapace width-at-age data for each sex in Cockburn Sound and the Peel-Harvey Estuary, in which recruitment occurs at an early age, were then described using a seasonal von Bertalanffy growth curve. The results demonstrated that the growth rates of P. pelagicus differed significantly neither between females and males nor between crabs in the two water bodies and that growth was highly seasonal, with little or no increase in size occurring during the cold winter and early spring months. They also showed that relatively few P. pelagicus live beyond 18 months and indicate that, as a result of legal restrictions against retaining ovigerous crabs and the poor quality of recently-moulted females, fishing mortality is far lower amongst female than male crabs. The fact that the carapace widths attained by P. pelagicus at the end of its first year of life in Cockburn Sound (105 mm) and the Peel-Harvey Estuary (109 mm) were very similar to those in the Leschenault Estuary (105 mm) and Koombana Bay (107 mm) into which that estuary discharges emphasizes that the growth of P. pelagicus in each of these systems was similar. Data are also presented which strongly indicate that the second moult undergone by mature females is accompanied by an increase in the relative size of the abdominal flap.