bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased expression of OCIA domain containing 2 during stepwise progression of ovarian mucinous tumor
Authors: Nagata Chigusa , Kobayashi Hiromi , Sakata Akiko , Satomi Kaishi , Minami Yuko , Morishita Yukio , Ohara Rena , Yoshikawa Hiroyuki , Arai Yuko , Nishida Masato , Noguchi Masayuki
Published: May 2012

Ovarian cancer immunoreactive antigen domain containing 2 (OCIAD2) has been reported to show cancer‐specific expression in early invasive lung adenocarcinoma. OCIAD2 shows high homology with OCIAD1, which was originally immunoscreened from ascites of a patient with ovarian cancer and found to be a tumor‐specific protein. Therefore, like OCIAD1, OCIAD2 is expected to show high immunoreactivity in ovarian tumors. In this study, we examined the expression pattern of OCIAD2 in 117 ovarian mucinous tumors, and confirmed that it was more highly expressed in borderline tumor and carcinoma (51/74 cases, 69%) than in adenoma (6/43 cases, 14%). The immunoreactivity of OCIAD2 in borderline tumor and carcinoma was more specific than that of OCIAD1 (adenoma, 21/43 cases, 49%), and more sensitive than that of CEA (borderline tumor and carcinoma, 35/74 cases, 47%). Like OCIAD1, OCIAD2 is a cancer‐related protein and its expression level increases during the course of malignant progression and is thought to be a very useful marker for evaluating the malignancy of ovarian mucinous tumors.
Cytoreductive nephrectomy for pT3b–T4 M1 renal cell carcinoma in 39 patients: Single center analysis
Authors: Takagi Toshio , Kondo Tsunenori , Iizuka Junpei , Kobayashi Hirohito , Hashimoto Yasunobu , Tanabe Kazunari
Published: May 2012

We reviewed cytoreductive nephrectomy for pT3b–T4 renal cell carcinoma with metastasis and evaluated the prognostic factors for cancer‐specific survival. A total of 39 patients who underwent cytoreductive nephrectomy for renal cell carcinoma with pathological T3b–T4 (2009 Union for International Cancer Control consensus) from 1986 to 2011 in our hospital were the participants in this study. Prognostic factors for cancer‐specific survival were analyzed. The median patient age was 64 years (range 31–84). Pathological T3b, T3c and T4 were found in 24 (61%), one (3%) and 14 (36%) patients, respectively. The distribution of the histological type was clear cell type in 34 (87%), papillary type in two (5%) and any type of renal cell carcinoma with a sarcomatoid component in three patients (8%). The median overall and cancer‐specific survival was 7.5 and 7.6 months, respectively. Low‐grade performance status, regional lymph node metastasis, higher pT stage and histological type were prognostic factors for cancer‐specific survival on univariate analysis. On multivariate analysis, lymph node metastasis, higher pT stage and histological type (non‐clear cell or sarcomatoid component) were significant predictors for cancer‐specific survival. With cytoreductive nephrectomy for patients with pT4, lymph node metastasis and non‐clear cell histology, we have to be particularly careful in terms of cancer control.
Nest habitat selection by the Austral parakeet in north‐western Patagonia
Authors: DÍAZ SOLEDAD , KITZBERGER THOMAS
Published: May 2012

Identifying habitat or nesting microhabitat variables associated with high levels of nest success is important to understand nest site preferences and bird–habitat relationships. Little is known about cavity availability and nest site requirements of cavity nesters in southern hemisphere temperate forests, although nest site limitation is suggested. Here we ask which characteristics are selected by the Austral parakeet (Enicognathus ferrugineus) for nesting in Araucaria araucana–Nothofagus pumilio forest in Argentine Patagonia. We compared nest plot and tree characteristics with unused plots and trees among areas of different A. araucana–N. pumilio density. We also examine whether nest plot and tree use and selection, and the associated consequences for fitness of Austral parakeets are spatially related to forest composition. Austral parakeets showed selectivity for nests at different spatial scales, consistently choosing isolated live and large trees with particular nest features in a non‐random way from available cavities. Mixed A. araucana–N. pumilio forests are ideal habitat for the Austral parakeets of northern Patagonia, offering numerous potential cavities, mainly in N. pumilio. We argue that Austral parakeet reproduction and fitness is currently very unlikely to be limited by cavity availability, although this situation may be rapidly changing. Natural and human disturbances are modifying south temperate forests with even‐aged mid‐successional stands replacing old growth forests. Cavity nesting species use and need old growth forests, due to the abundance of cavities in large trees and the abundance of larvae in old wood. Neither of the latter resources is sufficiently abundant in mid‐successional forests, increasing the vulnerability and threatening the survival of the Austral.
Complete remission after neoadjuvant chemotherapy of an advanced vulvar cancer patient: A case report
Authors: Achilli Chiara , Palaia Innocenza , Perniola Giorgia , Di Donato Violante , Marchetti Claudia , Benedetti Panici Pierluigi
Published: May 2012

Invasive vulvar cancer has an incidence of 1–2/100 000 women per year and squamous cell carcinoma accounts for approximately 85–90% of all vulvar cancers. Surgery has long been considered as the standard treatment, followed by chemotherapy in case of lymph node involvement. This approach is not only disfiguring, but also carries with it an operative mortality of up to 10%. Several studies have assessed the feasibility of radio‐chemotherapy as definitive therapy and/or a neoadjuvant procedure. Nonetheless, combined radio‐chemotherapy is associated with considerable toxicity. This study reports our experience with an unconventional schedule of neoadjuvant chemotherapy (topotecan and cisplatin) without radiotherapy in a patient with locally advanced vulvar cancer (International Federation of Gynecology and Obstetrics stage IIIA) who experienced complete clinical remission, followed by minimal surgical treatment.
Alterations of maternal serum and placental follistatin‐like 3 and myostatin in pre‐eclampsia
Authors: Guo Jing , Tian Ting , Lu Donghong , Xia Guiyu , Wang Hanzhi , Dong Minyue
Published: May 2012

Aim:  To clarify the alterations of myostatin, a member of the transforming growth factor‐β superfamily, and follistatin‐like 3 (FSTL3), a binding protein for myostatin, in pre‐eclamptic women.

Methods:  Samples of blood and placenta were collected from 40 pre‐eclamptic women and 40 controls. The serum level and placental expression of FSTL3 and myostatin were determined with enzyme‐linked immunosorbent assay, real‐time polymerized chain reaction and western blotting.

Results:  The serum levels of myostatin and FSTL3 were significantly higher in pre‐eclamptic women than in the controls (P < 0.001 for both). Placental expression of myostatin and FSTL3 were also significantly increased in the pre‐eclamptic placenta compared with that of the controls (P < 0.001 for both); however, there were no significant differences in myostatin or FSTL3 in either the maternal serum or the placenta in women with mild or severe pre‐eclampsia (P > 0.05 for both).

Conclusion:  The serum levels and placental expression of myostatin and FSTL3 are elevated in pre‐eclampsia, suggesting the role of myostatin and its binding protein in pre‐eclampsia.
Carotid intima media thickness, brachial flow mediated dilation and previous history of gestational diabetes mellitus
Authors: Fakhrzadeh Hossein , Alatab Sudabeh , Sharifi Farshad , Mirarefein Mojde , Badamchizadeh Zohreh , Ghaderpanahi Maryam , Hashemi Taheri Amir Pejman , Larijani Bagher
Published: May 2012

Aim:  Gestational diabetes mellitus (GDM) is a common pregnancy condition with long‐term complications. We examined the association between inflammatory mediators and early atherosclerosis process by measuring the flow mediated dilatation (FMD) of brachial artery and carotid intima media thickness (CIMT) in women with previous GDM (pGDM).

Material and Methods:  Women with and without pGDM with an average of 4 years following the indexed pregnancy, participated in this study. Serum levels of IL‐6, hs‐CRP, adiponectin, homocystein and other biomedical parameters were measured. The existence of early atherogenesis process was evaluated by measuring CIMT and FMD.

Results:  HOMA‐IR and insulin were significantly higher in women with pGDM. Women with pGDM had slightly higher CIMT and significantly lower percent of brachial FMD. FMD and CIMT, adjusted for age and blood pressure, showed the same pattern. FMD showed no correlation with biochemical or inflammatory markers.

Conclusion:  Follow‐up of this group of women, who are at increased risk of cardiovascular disease, with FMD should be considered.
Value‐based medicine analysis on loop electrosurgical excision procedure and CO2 laser vaporization for the treatment of cervical intraepithelial neoplasia 2
Authors: Sun Lu‐lu , Cao Dong‐yan , Yang Jia‐xin , Bian Mei‐lu , Wei Li‐hui , Shen Keng
Published: May 2012

Aim:  The best treatment option for cervical intraepithelial neoplasia 2 (CIN2) is controversial and there is a lack of studies in value‐based medicine. This multicenter comparative study was undertaken to evaluate the effectiveness, cost‐effectives and quality of life (QOL) of loop electrosurgical excision procedure (LEEP) and CO2 laser vaporization for the treatment of CIN2.

Material and Methods:  A database of LEEP and laser vaporizations performed at three research centers was created. Patients with colposcopic‐histopathologically confirmed CIN2 were randomly submitted to LEEP and laser vaporization. Cytology, human papilloma virus (HPV) DNA test and histology were performed, and a questionnaire on QOL was filled out during follow‐up. Effectiveness, cost‐effectives and QOL were analyzed.

Results:  Three hundred and thirty‐eight women with CIN2 were included in the study. Frequencies of remission, and persistent and recurrent CIN were 89.2%, 7.2%, and 3.6% for LEEP, and 86.7%, 12.6%, 0.70% for laser, respectively. There was no significant difference in remission and persistence of CIN. There was a significant difference in the number of operations, recovery time and costs. Women treated with two methods showed relatively identical QOL.

Conclusion:  Both LEEP and CO2 laser vaporization are effective and reliable treatments for CIN2, whereas cervical tissue can be obtained for histology by LEEP. Preoperative evaluation and postoperative follow‐up are important. Gynecologists should pay attention to QOL of patients with CIN.
Antenatal differential diagnosis of congenital chloride diarrhea: A case report
Authors: Lee Dae Hyung , Park Yoon Ki
Published: May 2012

Congenital chloride diarrhea (CCD) is a rare disease characterized by profound, watery diarrhea. It is inherited as an autosomal recessive trait and is caused by a dysfunction of electrolyte transport in the brush border of the ileum. CCD is a medically treatable condition but is frequently misdiagnosed as a surgically treatable condition, such as bowel obstruction, because of similar antenatal ultrasonographic findings. Therefore, a correct diagnosis is of upmost importance before treatment initiation. Although some methods for antenatal differential diagnosis were reported, antenatal diagnosis of CCD remains difficult. Here, we report the case of a patient with CCD, which was presumed antenatally and confirmed postnatally. We also discuss the results of antenatal ultrasonography and amniocentesis and provide some tips regarding ultrasonographic findings for the antenatal differential diagnosis of CCD. Further, we present a brief literature review.
The metagenome of the marine anammox bacterium ‘Candidatus Scalindua profunda’ illustrates the versatility of this globally important nitrogen cycle bacterium
Authors: van de Vossenberg Jack , Woebken Dagmar , Maalcke Wouter J. , Wessels Hans J. C. T. , Dutilh Bas E. , Kartal Boran , Janssen‐Megens Eva M. , Roeselers Guus , Yan Jia , Speth Daan , Gloerich Jolein , Geerts Wim , van der Biezen Erwin , Pluk Wendy , Francoijs Kees‐Jan , Russ Lina , Lam Phyllis , Malfatti Stefanie A. , Tringe Susannah Green , Haaijer Suzanne C. M. , Op den Camp Huub J. M. , Stunnenberg Henk G. , Amann Rudi , Kuypers Marcel M. M. , Jetten Mike S. M.
Published: May 2012

Anaerobic ammonium‐oxidizing (anammox) bacteria are responsible for a significant portion of the loss of fixed nitrogen from the oceans, making them important players in the global nitrogen cycle. To date, marine anammox bacteria found in marine water columns and sediments worldwide belong almost exclusively to the ‘Candidatus Scalindua’ species, but the molecular basis of their metabolism and competitive fitness is presently unknown. We applied community sequencing of a marine anammox enrichment culture dominated by ‘Candidatus Scalindua profunda’ to construct a genome assembly, which was subsequently used to analyse the most abundant gene transcripts and proteins. In the S. profunda assembly, 4756 genes were annotated, and only about half of them showed the highest identity to the only other anammox bacterium of which a metagenome assembly had been constructed so far, the freshwater ‘Candidatus Kuenenia stuttgartiensis’. In total, 2016 genes of S. profunda could not be matched to the K. stuttgartiensis metagenome assembly at all, and a similar number of genes in K. stuttgartiensis could not be found in S. profunda. Most of these genes did not have a known function but 98 expressed genes could be attributed to oligopeptide transport, amino acid metabolism, use of organic acids and electron transport. On the basis of the S. profunda metagenome, and environmental metagenome data, we observed pronounced differences in the gene organization and expression of important anammox enzymes, such as hydrazine synthase (HzsAB), nitrite reductase (NirS) and inorganic nitrogen transport proteins. Adaptations of Scalindua to the substrate limitation of the ocean may include highly expressed ammonium, nitrite and oligopeptide transport systems and pathways for the transport, oxidation, and assimilation of small organic compounds that may allow a more versatile lifestyle contributing to the competitive fitness of Scalindua in the marine realm.
L‐dopa decarboxylase (DDC) gene expression is related to outcome in patients with prostate cancer
Authors: Koutalellis Georgios , Stravodimos Konstantinos , Avgeris Margaritis , Mavridis Konstantinos , Scorilas Andreas , Lazaris Andreas , Constantinides Constantinos
Published: May 2012

What's known on the subject? and What does the study add?

L‐dopa decarboxylase (DDC) has been documented as a novel co‐activator of androgen receptor transcriptional activity. Recently, it was shown that DDC gene expression is significantly higher in patients with PCa than in those with BPH.

In the present study, there was a significant association between the DDC gene expression levels and the pathological stage and Gleason score of patients with prostate cancer (PCa). Moreover, DDC expression was shown to be an unfavourable prognostic marker of biochemical recurrence and disease‐free survival in patients with PCa treated by radical prostatectomy.

OBJECTIVE

To determine whether L‐dopa decarboxylase gene (DDC) expression levels in patients with prostate cancer (PCa) correlate to biochemical recurrence and disease prognosis after radical prostatectomy (RP).

PATIENTS AND METHODS

The present study consisted of 56 samples with confirmed malignancy from patients with PCa who had undergone RP at a single tertiary academic centre.

Total RNA was isolated from tissue specimens and a SYBR Green fluorescence‐based quantitative real‐time polymerase chain reaction methodology was developed for the determination of DDC mRNA expression levels of the tested tissues.

Follow‐up time ranged between 1.0 and 62.0 months (mean ± SE, 28.6 ± 2.1 month; median, 31.5 months). Time to biochemical recurrence was defined as the interval between the surgery and the measurement of two consecutive values of prostate‐specific antigen (PSA) ≥0.2 ng/mL.

RESULTS

DDC expression levels were found to be positively correlated with the tumour‐node‐metastasis stage (P= 0.021) and Gleason score (P= 0.036) of the patients with PCa.

Patients with PCa with raised DDC expression levels run a significantly higher risk of biochemical recurrence after RP, as indicated by Cox proportional regression analysis (P= 0.021).

Multivariate Cox proportional regression models revealed the preoperative PSA‐, age‐ and digital rectal examination‐independent prognostic value of DDC expression for the prediction of disease‐free survival (DFS) among patients with PCa (P= 0.036).

Kaplan–Meier survival analysis confirms the significantly shorter DFS after RP of PCa with higher DDC expression levels (P= 0.015).

CONCLUSIONS

This is the first study indicating the potential of DDC expression as a novel prognostic biomarker in patients with PCa who have undergone RP.

For further evaluation and clinical application of the findings of the present study, a direct analysis of mRNA and/or its protein expression level in preoperative biopsy, blood serum and urine should be conducted.
Ciliary function in the olfactory organs of sharks and rays
Authors: Cox Jonathan P L
Published: May 2012

The sensory channels in the olfactory organs of modern sharks and rays (neoselachians) are lined with fields of non‐sensory cilia. Using evidence from 31 species of neoselachian, this review attempts to identify the fluid – water or mucus – propelled by these cilia. The apparently common structure of the olfactory epithelium in these 31 diverse species implies that the cilia perform the same function and that this function is therefore independent of neoselachian phylogeny, lifestyle, gross nasal anatomy and the principal means by which water is circulated through the single major olfactory channel. On balance, the evidence suggests that the cilia propel mucus. This evidence includes short cilia, the presence (or absence) of water currents in the nasal region, mucociliary interactions, poor ciliary alignment, rare or absent interciliary connections, deep ciliary anchorages and the observation of cilia performing effective strokes. The short cilia are particularly telling. Goblet cells within and on the edge of the sensory epithelium are likely to be the source of any mucus layer. If the cilia of the neoselachian olfactory epithelium do propel mucus, there are three crucial implications. First, given that ciliary function is potentially independent of neoselachian phylogeny, it is possible that cilia in all neoselachians propel mucus. Second, a large part of the neoselachian olfactory organ must be actively involved in protecting the sensory epithelium from damage. Third, flow of water through the sensory channels must be driven by flow of water through the major olfactory channel.
Modelling obesity trends and related diseases in Eastern Europe
Authors: Webber L. , Kilpi F. , Marsh T. , Rtveladze K. , McPherson K. , Brown M.
Published: May 2012

Obesity has increased at an alarming rate across the world and, in turn, rates of non‐communicable diseases have escalated. In Eastern Europe, this epidemic has probably occurred at a later stage than the West due to the economic transition following the demise of communism. Knowing how these trends will change is important. We used a micro‐simulation model to project obesity trends and related incidence of coronary heart disease and stroke, cancer and type 2 diabetes 20 and 40 years into the future. Where nationally representative data were available, obesity levels were shown to increase with most prominent increases seen amongst men in Latvia and Estonia, and amongst women in Croatia and Latvia. The exception was Lithuania where a decrease in overweight and obesity was observed in both men and women. We showed that interventions effective in reducing obesity would have a significant impact upon the number of new cases of each disease. It is necessary to improve surveillance of obesity and disease incidence as well as implement policies that are effective in reducing body fat.
Resting energy expenditure of morbidly obese patients using indirect calorimetry: a systematic review
Authors: Kee A.‐L. , Isenring E. , Hickman I. , Vivanti A.
Published: May 2012

The increasing proportion of acutely ill hospital patient admissions presenting with a morbidly obese body mass index (BMI ≥ 40 kg m−2) as a comorbidity is an emerging clinical concern. Suboptimal food intake and malnutrition is prevalent in the acute care hospital setting. The energy requirements necessary to prevent malnutrition in acutely ill patients with morbid obesity remains unclear. The aim of this systematic review was to identify studies in the literature that have used indirect calorimetry to measure the resting energy expenditure of patients with morbid obesity to establish their minimum energy requirements and the implications for optimal feeding practices in acutely ill hospitalized patients. A total of 20 studies from PubMed, Cochrane Library and Embase met the inclusion criteria and were reviewed. All articles were graded using the Australian National Health and Medical Research Council levels of evidence and given a quality rating using the American Dietetic Association recommendations. Studies were categorized according to the mean BMI of its subjects. The most commonly measured resting energy expenditures for morbidly obese patients are between 2,000 and 3,000 kcal d−1 (8,400–12,600 kJ d−1). Activity and injury factors of acutely ill morbidly obese patients could result in significantly greater energy requirements for this patient group and are unlikely to be met by standard hospital menus. Establishing the minimum energy requirements for this population group will help inform adequate and accurate energy provision in the acute setting. Outcomes of underfeeding and overfeeding in morbidly obese patients warrant further research.
TeamArab:al‐Jazeeraand the flagging of everydayArabism during the 2008BeijingOlympics
Authors: Phillips Christopher
Published: May 2012

The linking of living rooms across state borders byal‐Jazeera and other pan‐Arab satellite television channels has prompted claims that a ‘newArabism’ that undermines state nationalism is emerging. Until now, analysts have mostly focused on the ‘hot’Arabism in the news coverage of politicised events such as theIsrael–Palestine conflict. This article offers a new dimension by suggesting that as important to satellite television's construction and reproduction ofArab identity is the everyday discourse found in less overtly political programmes such as sport. To demonstrate this, it offers an analysis of al‐Jazeera's coverage of the 2008BeijingOlympics showing how the broadcasts address viewers as a commonArab audience who are simultaneously encouraged to be nationalistic towards their separate nation‐states within a given ‘Arab arena’ of states with whom they should primarily compete. This suggests that new Arabism should in fact be considered a ‘supranationalism’, not a revived Arab nationalism as it simultaneously promotes Arab and state identities in tandem. Finally, it aims to expand our understanding of ‘everyday nationalism’ by adaptingMichaelBillig's theory and methodology of ‘banal nationalism’ inBritish newspapers to facilitate the study of sport on supranational Arab identity on satellite television.
Quiet eye training expedites motor learning and aids performance under heightened anxiety: The roles of response programming and external attention
Authors: Moore Lee J. , Vine Samuel J. , Cooke Andrew , Ring Christopher , Wilson Mark R.
Published: May 2012

Quiet eye training expedites skill learning and facilitates anxiety‐resistant performance. Changes in response programming and external focus of attention may explain such benefits. We examined the effects of quiet eye training on golf‐putting performance, quiet eye duration, kinematics (clubhead acceleration), and physiological (heart rate, muscle activity) responses. Forty participants were assigned to a quiet eye or technical trained group and completed 420 baseline, training, retention, and pressure putts. The quiet eye group performed more accurately and displayed more effective gaze control, lower clubhead acceleration, greater heart rate deceleration, and reduced muscle activity than the technical trained group during retention and pressure tests. Thus, quiet eye training was linked to indirect measures of improved response programming and an external focus. Mediation analyses partially endorsed a response programming explanation.
Having a Pap smear, quality of life before and after cervical screening: a questionnaire study
Authors: Korfage IJ , van Ballegooijen M , Wauben B , Looman CWN , Habbema JDF , Essink‐Bot M‐L
Published: May 2012

Please cite this paper as: Korfage I, van Ballegooijen M, Wauben B, Looman C, Habbema J, Essink‐Bot M. Having a Pap smear, quality of life before and after cervical screening: a questionnaire study. BJOG 2012;119:936–944.

Objective  To assess the health‐related quality of life (HRQoL) impact of cervical cancer screening in women with normal test results.

Design  Questionnaire study.

Setting  Maastricht, the Netherlands.

Population  A cohort of 789 women were followed from screening invitation until after the receipt of screening results. A female age‐matched reference group (n = 567) was included.

Methods  Questionnaires were sent to the home address of the women before screening, after screening, and again with the screening results.

Main outcome measures  Generic HRQoL (SF‐12, EQ‐5D), generic anxiety (STAI‐6), screen‐specific anxiety (PCQ), and potential symptoms and feelings related to the smear‐taking procedure.

Results  A total of 60% of screening participants completed questionnaire 1(n = 924): 803 of these women granted permission to access their files; 789 of these 803 women had normal test results (Pap 1), and were included in the analyses. Generic HRQoL (SF‐12, EQ‐5D) and anxiety (STAI‐6) scores were similar in the study and reference groups. Before screening, after screening, and also after the receipt of test results, screening participants reported less screen‐specific anxiety (PCQ, P < 0.001) than the reference group (n = 567), with differences indicating clinical relevance. 19% of screening participants were bothered by feelings of shame, pain, inconvenience, or nervousness during smear taking, and 8 and 5% of women experienced lower abdominal pain, vaginal bleeding, discharge, or urinary problems for 2–3 and 4–7 days, respectively, following the Pap smear.

Conclusion  The reduced levels of screen‐specific anxiety in screening participants, possibly indicating reassurance, are worthwhile addressing in more depth. We conclude that although considerable numbers of women reported unpleasant effects, there were no adverse HRQoL consequences of cervical screening in women with normal test results.
Low‐molecular‐weight heparin or warfarin for anticoagulation in pregnant women with mechanical heart valves: what are the risks? A retrospective observational study
Authors: Basude S , Hein C , Curtis SL , Clark A , Trinder J
Published: May 2012

Please cite this paper as: Basude S, Hein C, Curtis S, Clark A, Trinder J. Low‐molecular‐weight heparin or warfarin for anticoagulation in pregnant women with mechanical heart valves: what are the risks? A retrospective observational study. BJOG 2012;119:1008–1013.

The management of anticoagulation in pregnant women with mechanical heart valves is complex. The maternal and fetal outcomes of 32 pregnancies in 15 women on three different anticoagulation regimens were compared. Anticoagulation with low‐molecular‐weight heparin (n = 4), warfarin (n = 22) and combination therapy (n = 6) resulted in adverse maternal events in four (100%), three (50%) and three (14%) women, and resulted in fetal losses in one (25%), 17(77%) and three (50%) pregnancies, respectively. Whereas the rate of fetal loss in the warfarin group was high, all women in the LMWH and half of those in the combination group had serious adverse maternal events, including valve thrombosis, maternal death and postpartum haemorrhage.
Application of cardiac electrophysiology simulations to pro‐arrhythmic safety testing
Authors: Mirams Gary R , Davies Mark R , Cui Yi , Kohl Peter , Noble Denis
Published: May 2012

Concerns over cardiac side effects are the largest single cause of compound attrition during pharmaceutical drug development. For a number of years, biophysically detailed mathematical models of cardiac electrical activity have been used to explore how a compound, interfering with specific ion‐channel function, may explain effects at the cell‐, tissue‐ and organ‐scales. With the advent of high‐throughput screening of multiple ion channels in the wet‐lab, and improvements in computational modelling of their effects on cardiac cell activity, more reliable prediction of pro‐arrhythmic risk is becoming possible at the earliest stages of drug development. In this paper, we review the current use of biophysically detailed mathematical models of cardiac myocyte electrical activity in drug safety testing, and suggest future directions to employ the full potential of this approach.

LINKED ARTICLE This article is commented on by Gintant, pp. 929–931 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2012.02096.x
The stereotypy‐inducing and OCD‐like effects of chronic ‘binge’ cocaine are modulated by distinct subtypes of nicotinic acetylcholine receptors
Authors: Metaxas A , Keyworth HL , Yoo JH , Chen Y , Kitchen I , Bailey A
Published: May 2012

BACKGROUND AND PURPOSE High rates of cigarette smoking occur in cocaine‐dependent individuals, reflecting an involvement of nicotinic acetylcholine receptors (nAChRs) in cocaine‐elicited behaviour. This study was designed to assess the contribution of different nAChR subtypes to the behavioural and neurochemical effects of chronic cocaine treatment.

EXPERIMENTAL APPROACH Cocaine (15 mg·kg−1, i.p.) was administered to male C57BL/6J mice in a chronic ‘binge’ paradigm, with and without the coadministration of the α7 preferring nAChR antagonist methyllycaconitine (MLA; 5 mg·kg−1, i.p.) or the β2* nAChR antagonist dihydro‐β‐erythroidine (DHβE; 2 mg·kg−1, i.p.). Quantitative autoradiography was used to examine the effect of cocaine exposure on α7 and α4β2* nAChRs, and on the high‐affinity choline transporter.

KEY RESULTS MLA+cocaine administration induced an intense self‐grooming behaviour, indicating a likely role for α7 nAChRs in modulating this anxiogenic, compulsive‐like effect of cocaine. In the major island of Calleja, a key area of action for neuroleptics, MLA+cocaine reduced choline transporter binding compared with cocaine (with or without DHβE) administration. DHβE treatment prevented the induction of stereotypy sensitisation to cocaine but prolonged locomotor sensitisation, implicating heteromeric β2* nAChRs in the neuroadaptations mediating cocaine‐induced behavioural sensitisation. ‘Binge’ cocaine treatment region‐specifically increased α4β2* nAChR binding in the midbrain dopaminergic regions: ventral tegmental area and substantia nigra pars compacta.

CONCLUSIONS AND IMPLICATIONS We have shown a differential, subtype‐selective, contribution of nAChRs to the behavioural and neurochemical sequelae of chronic cocaine administration. These data support the clinical utility of targeting specific nAChR subtypes for the alleviation of cocaine‐abuse symptomatology.
Tale of the Kulet eclogite from the Kokchetav Massive, Kazakhstan: Initial tectonic setting and transition from amphibolite to eclogite
Authors: ZHANG R. Y. , LIOU J. G. , OMORI S. , SOBOLEV N. V. , SHATSKY V. S. , IIZUKA Y. , LO C.‐H. , OGASAWARA Y.
Published: May 2012

The Kulet eclogite in the Kokchetav Massif, northern Kazakhstan, is identified as recording a prograde transformation from the amphibolite facies through transitional coronal eclogite to fully recrystallized eclogite (normal eclogite). In addition to minor bodies of normal eclogite with an assemblage of Grt + Omp + Qz + Rt ± Ph and fine‐grained granoblastic texture (type A), most are pale greyish green bodies consisting of both coronal and normal eclogites (type B). The coronal eclogite is characterized by coarse‐grained amphibole and zoisite of amphibolite facies, and the growth of garnet corona along phase boundaries between amphibole and other minerals as well as the presence of eclogitic domains. The Kulet eclogites experienced a four‐stage metamorphic evolution: (I) pre‐eclogite stage, (II) transition from amphibolite to eclogite, (III) a peak eclogite stage with prograde transformation from coronal eclogite to UHP eclogite and (IV) retrograde metamorphism. Previous studies made no mention of the presence of amphibole or zoisite in either the pre‐eclogite stage or coronal eclogite, and so did not identify the four‐stage evolution recognized here. P–T estimates using thermobarometry and Xprp and Xgrs isopleths of eclogitic garnet yield a clockwise P–T path and peak conditions of 27–33 kbar and 610–720 °C, and 27–35 kbar and 560–720 °C, respectively. P–T pseudosection calculations indicate that the coexistence of coronal and normal eclogites in a single body is chiefly due to different bulk compositions of eclogite. All eclogites have tholeiitic composition, and show flat or slightly LREE‐enriched patterns [(La/Lu)N = 1.1–9.6] and negative Ba, Sr and Sc and positive Th, U and Ti anomalies. However, normal eclogite has higher TiO2 (1.35–2.65 wt%) and FeO (12.11–16.72 wt%) and REE contents than those of coronal eclogite (TiO2 < 0.9 wt% and FeO < 12.11 wt%) with one exception. Most Kulet eclogites plot in the MORB and IAB fields in the 2Nb–Zr/4–Y and TiO2–FeO/MgO diagrams, although displacement from the MORB–OIB array indicates some degree of crustal involvement. All available data suggest that the protoliths of the Kulet eclogites were formed at a passive continent marginal basin setting. A schematic model involving subduction to 180–200 km at 537–527 Ma, followed by slab breakoff at 526–507 Ma, exhumation and recrystallization at crustal depths is applied to explain the four‐stage evolution of the Kulet eclogite.
The Relationship Between Alcohol Consumption and Fatal Motor Vehicle Injury: High Risk at Low Alcohol Levels
Authors: Taylor Benjamin , Rehm Jürgen
Published: May 2012

Background

Alcohol consumption causes motor vehicle accident (MVA) injury in a dose–response fashion. However, the relationship between how this risk is different with respect to fatal and nonfatal outcomes is not clear. A meta‐analysis has already been completed for alcohol consumption and nonfatal MVA injury, but none exists for fatal injury. Thus, an analysis of the acute dose–response relationship between alcohol and motor vehicle injury death is warranted to generate single occasion‐ and dose‐specific relative risks for the first time.

Methods

A systematic literature review and inverse‐variance weighted, random effects meta‐analysis were conducted to fill this gap. Fractional polynomial regression was used to model the dose–response relationship. Usual tests of heterogeneity and publication bias were run.

Results

Five studies meeting the inclusion criteria of this analysis were selected. At all levels of blood alcohol concentration (BAC), the odds ratio (OR) of fatal motor vehicle injury was significant. Overall, the 5 combined studies yielded an OR of fatal injury of 1.74 (95% CI: 1.43–2.14) for every 0.02% increase in BAC. At 0.08, the legal limit in most countries, the OR was 13.0 (95% CI: 11.1–15.2).

Conclusions

This study is able to definitively show and quantify, for the first time, the significantly increased OR for fatal motor vehicle injury. This analysis showed some evidence of both study heterogeneity and publication bias, likely due to the increased variation we could expect from a small study number. The alcohol‐caused fatal motor vehicle injury literature is sparse with respect to dose–response information. More studies investigating this relationship and other injury types are recommended in this area to be able to calculate stable estimates of risk overall and by injury type specifically.
Characterization of Cerebellar Ataxia in Chronic Alcoholics Using the International Cooperative Ataxia Rating Scale (ICARS)
Authors: Fitzpatrick Lauren E. , Jackson Martin , Crowe Simon F.
Published: May 2012

Background

Alcoholism is the most common cause of cerebellar dysfunction, yet estimates of the incidence of alcoholic cerebellar degeneration (ACD) vary greatly, with differences in methodologies contributing to these disparate findings. This study set out to characterize the frequency and pattern of clinical signs of ACD in an alcoholic group using the International Cooperative Ataxia Rating Scale (ICARS).

Methods

We compared the performance of 49 alcoholics and 29 control participants. The relative contributions of demographic and alcohol consumption variables to ICARS scores in the alcoholic group were also examined.

Results

The alcoholic group demonstrated significantly poorer performance on all of the ICARS subscales as compared with the control group. Within the alcoholic group, performance was more impaired on the speech scale than on all of the other scales, except the lower limb component of the kinetic scale, and less impaired on the oculomotor scale compared with all other scales. Years of heavy drinking and lifetime alcohol consumption correlated with total ICARS scores; however, maximum daily consumption was actually negatively correlated with ICARS scores. Of the alcohol history variables, years of heavy drinking was the best predictor of total ICARS scores, making a 19% unique contribution, followed by the period of abstinence from alcohol, which uniquely contributed 7% of the variance. There were high correlations between age and male gender and the alcohol consumption variables; however, age and gender were still found to uniquely contribute 5 and 7% respectively to the variance in total ICARS scores.

Conclusions

ACD may affect up to two‐thirds of chronic alcoholics. Assessing the number of years an individual has been drinking beyond a certain threshold can give a good indication of the likelihood of ACD. Age, gender, and the source of the clinical sample may significantly contribute to the prevalence of ACD and require further detailed investigation.
Commentary on the Study: Impact of Depressive Symptoms on Future Alcohol Use in Patients with Co‐Occurring Bipolar Disorder and Alcohol Dependence: A Prospective Analysis in an 8‐Week Randomized Controlled Trial of Acamprosate (Prisciandaro et al.)
Authors: Preuss Ulrich W.
Published: May 2012

Background

Comorbidity of alcohol abuse and dependence with bipolar disorders is high. The aim of this short commentary is to review a current study investigating the impact of depressive symptoms and craving on alcohol use in individuals with co‐occurring bipolar disorder and alcohol dependence.

Methods

The strengths of Prisciandaro and colleagues' (2012) study are reviewed. The research group collected data as part of an 8‐week, randomized, double‐blind, placebo‐controlled trial of acamprosate treatment in comorbid individuals.

Results

The importance of the study lies in highlighting the complex relationship between bipolar affective disorder symptoms, in particular depression, and alcohol use in a prospective design. It also overcomes several shortcomings of previous studies, since trajectories of both disorders within a short time frame of 1 week were hitherto rarely investigated.

Conclusions

While the current study is successfully shedding light on the relationship between depressive symptoms, craving, and alcohol use in comorbid individuals, future studies may also investigate the influence of rapid cycling, mixed states, and psychotic symptoms on alcohol consumption and vice versa. Further, other comorbid samples could be included like first episode versus subjects with multiple affective episodes or comorbidity in males versus females. This research may provide a better basis for future psychotherapy and pharmacotherapy or integrated treatment approaches in these comorbid and severely affected individuals.
The Role of Empathy in Responding to Natural Disasters: Comment on “Who Helps Natural Disaster Victims?”
Authors: Banfield Jillian C. , Dovidio John F.
Published: May 2012

Comment on Marjanovic, Struthers, and Greenglass (2012). We build on the authors’ ideas, data, and interpretations to suggest future avenues for research, focusing on situations that hold potential for empathic concern to shape helping responses. Specifically, we suggest investigating the time course of reactions to natural disasters and the group membership of the victims as moderators. Additionally, we suggest that considering different forms of helping responses and their predictors can shed theoretical light on variables that promote helping following natural disasters.
Assessing the Environmental Impact of Water Consumption by Energy Crops Grown in Spain
Authors: Núñez Montserrat , Pfister Stephan , Antón Assumpció , Muñoz Pere , Hellweg Stefanie , Koehler Annette , Rieradevall Joan
Published: May 2012

The environmental impact of the water consumption of four typical crop rotations grown in Spain, including energy crops, was analyzed and compared against Spanish agricultural and natural reference situations. The life cycle assessment (LCA) methodology was used for the assessment of the potential environmental impact of blue water (withdrawal from water bodies) and green water (uptake of soil moisture) consumption. The latter has so far been disregarded in LCA. To account for green water, two approaches have been applied: the first accounts for the difference in green water demand of the crops and a reference situation. The second is a green water scarcity index, which measures the fraction of the soil‐water plant consumption to the available green water. Our results show that, if the aim is to minimize the environmental impacts of water consumption, the energy crop rotations assessed in this study were most suitable in basins in the northeast of Spain. In contrast, the energy crops grown in basins in the southeast of Spain were associated with the greatest environmental impacts. Further research into the integration of quantitative green water assessment in LCA is crucial in studies of systems with a high dependence on green water resources.
An Approach for Calculating the Environmental External Costs of the Belgian Building Sector
Authors: Allacker Karen , De Nocker Leo
Published: May 2012

This article describes an approach developed to estimate the environmental external costs of the Belgian building sector. Several existing methods and related data sets for determining the monetary value of environmental impacts were reviewed and compared in light of their relevance to an impact assessment of the construction sector. This study concludes that the methods available consider different impacts and differ substantially in monetary values for identical impacts. A harmonized and transparent method is recommended to improve the feasibility and acceptance of internalizing external costs; agreement on the impacts to be assessed and their external costs based on current insights is important. Here, a new method is proposed for a life cycle impact assessment‐based valuation of environmental external costs for application to the Belgian building sector. To enable a comprehensive assessment, it became clear that solely considering “key” pollutants is insufficient.

Although this article focuses on the development and not on the implementation of the method proposed, implementation revealed that the life cycle environmental external cost of new buildings (meeting current insulation standards or better) is relatively small compared to the life cycle financial cost.
Antidepressant Use, Depressive Symptoms, and Incident Frailty in Women Aged 65 and Older from the Women's Health Initiative Observational Study
Authors: Lakey Susan L. , LaCroix Andrea Z. , Gray Shelly L. , Borson Soo , Williams Carla D. , Calhoun Darren , Goveas Joseph S. , Smoller Jordan W. , Ockene Judith K. , Masaki Kamal H. , Coday Mace , Rosal Milagros C. , Woods Nancy F.
Published: May 2012

Objectives

To examine the associations between depressive symptoms, antidepressant use, and duration of use with incident frailty 3 years later in nonfrail women aged 65 and older.

Design

Secondary analysis of the Women's Health Initiative Observational Study (WHI‐OS), a prospective cohort study.

Setting

WHI‐OS was conducted in 40 U.S. clinical centers.

Participants

Women aged 65 to 79, not frail at baseline.

Measurements

Antidepressant use was assessed through medication container inspection at baseline. Four groups were created according to baseline use and Burnam depression screen (range 0–1, 0.06 cutoff): antidepressant nonusers without depressive symptoms (reference group), antidepressant nonusers with depressive symptoms, antidepressant users without depressive symptoms, and antidepressant users with depressive symptoms. Frailty components included slowness or weakness, exhaustion, low physical activity, and unintended weight loss, ascertained through self‐report and physical measurements at baseline and Year 3.

Results

Of 27,652 women at baseline, 1,350 (4.9%) were antidepressant users and 1,794 (6.5%) were categorized as depressed. At Year 3, 4,125 (14.9%) were frail. All groups had a greater risk of incident frailty than the reference group. Odds ratios (ORs) ranged from 1.73 (95% confidence interval (CI) = 1.41–2.12) in antidepressant users who were not depressed to 3.63 in antidepressant users who were depressed (95% CI = 2.37–5.55). All durations of use were associated with incident frailty (<1 year OR = 1.95, 95% CI = 1.41–2.68; 1–3 years OR = 1.99, 95% CI = 1.45–2.74; >3 years OR = 1.60, 95% CI = 1.20–2.14).

Conclusion

In older adult women, depressive symptoms and antidepressant use were associated with frailty after 3 years of follow‐up.
Summary Report from the Human Immunodeficiency Virus and Aging Consensus Project: Treatment Strategies for Clinicians Managing Older Individuals with the Human Immunodeficiency Virus
Authors:   Work Group for the HIV and Aging Consensus Project
Published: May 2012

By 2015, most of the people living with the human immunodeficiency virus (HIV) in the United States will be aged 50 and older. Many will have known their HIV status for at least a decade, and most will have received antiretroviral therapy for some, if not all, of the time since testing positive. As these individuals advance in years, they frequently acquire diseases more commonly associated with aging than with HIV. This represents a unique challenge for today's medical providers. Although these individuals may appear considerably older than their chronological age, they are typically too young to see a geriatrician. An HIV specialist, although knowledgeable in the nuances of antiretroviral therapy, may be less comfortable managing multiple age‐related illnesses. Similarly, a geriatrician experienced in managing multiple, age‐related conditions may be less familiar with adjusting HIV‐related therapies. In this era of caring for older adults with HIV, these two medical disciplines are finding they have much to learn from each other.