bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the etiology of acute kidney injury on outcomes following liver transplantation: acute tubular necrosis versus hepatorenal syndrome
Authors: Nadim Mitra K. , Genyk Yuri S. , Tokin Chris , Fieber Jenny , Ananthapanyasut Wanwarat , Ye Wei , Selby Rick
Published: January 2012

Acute kidney injury (AKI) at the time of liver transplantation (LT) has been associated with increased morbidity and mortality. In patients with potentially reversible renal dysfunction, predicting whether there will be sufficient return of native kidney function is sometimes difficult. Previous studies have focused mainly on the effect of the severity of renal dysfunction or the duration of pretransplant dialysis on posttransplant outcomes. We performed a retrospective analysis of patients who underwent LT at our center after Model for End-Stage Liver Disease–based allocation so that we could determine the impact of the etiology of AKI [acute tubular necrosis (ATN) versus hepatorenal syndrome (HRS)] on post-LT outcomes. The patients were stratified according to the severity of AKI at the time of LT as described by the Risk, Injury, Failure, Loss, and End-Stage Kidney Disease (RIFLE) classification: risk, injury, or failure. The RIFLE failure group was further subdivided according to the etiology of AKI: HRS or ATN. The patient survival and renal outcomes 1 and 5 years after LT were significantly worse for those with ATN. At 5 years, the incidence of chronic kidney disease (stage 4 or 5) was statistically higher in the ATN group versus the HRS group (56% versus 16%, P < 0.001). A multivariate analysis revealed that the presence of ATN at the time of LT was the only variable associated with higher mortality 1 year after LT (P < 0.001). Our study is the first to demonstrate that the etiology of AKI has the greatest impact on patient and renal outcomes after LT. Liver Transpl, 2012. © 2012 AASLD.
Predicting physical activity and fruit and vegetable intake in adolescents: A test of the information, motivation, behavioral skills model
Authors: Kelly Stephanie , Melnyk Bernadette Mazurek , Belyea Michael
Published: January 2012

Most adolescents do not meet national recommendations regarding physical activity and/or the intake of fruits and vegetables. The purpose of this study was to explore whether variables in the information, motivation, behavioral skills (IMB) model of health promotion predicted physical activity and fruit and vegetable intake in 404 adolescents from 2 high schools in the Southwest United States using structural equation modeling (SEM). The SEM models included theoretical constructs, contextual variables, and moderators. The theoretical relationships in the IMB model were confirmed and were moderated by gender and race. Interventions that incorporate cognitive‐behavioral skills building may be a key factor for promoting physical activity as well as fruit and vegetable intake in adolescents. © 2012 Wiley Periodicals, Inc. Res Nurs Health 35:146–163, 2012
In hepatocellular carcinoma miR‐519d is up‐regulated by p53 and DNA hypomethylation and targets CDKN1A/p21, PTEN, AKT3 and TIMP2
Authors: Fornari Francesca , Milazzo Maddalena , Chieco Pasquale , Negrini Massimo , Marasco Elena , Capranico Giovanni , Mantovani Vilma , Marinello Jessica , Sabbioni Silvia , Callegari Elisa , Cescon Matteo , Ravaioli Matteo , Croce Carlo M , Bolondi Luigi , Gramantieri Laura
Published: January 2012

MiR‐519d belongs to the chromosome 19 miRNA cluster (C19MC), the largest human miRNA cluster. One of its members, miR‐519d, is over‐expressed in hepatocellular carcinoma (HCC) and we characterized its contribution to hepatocarcinogenesis. In HCC cells, the over‐expression of miR‐519d promotes cell proliferation, invasion and impairs apoptosis following anticancer treatments. These functions are, at least in part, exerted through the direct targeting of CDKN1A/p21, PTEN, AKT3 and TIMP2. The mechanisms underlying miR‐519d aberrant expression in HCC were assayed by genomic DNA amplification, methylation analysis and ChIP assay. The aberrant hypomethylation of C19MC and TP53 were respectively identified as an epigenetic change allowing the aberrant expression of miR‐519d and one of the factors able to activate its transcription. In conclusion, we assessed the oncogenic role of miR‐519d in HCC by characterizing its biological functions, including the modulation of response to anticancer treatments and by identifying CDKN1A/p21, PTEN, AKT3 and TIMP2 among its targets. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
A policy framework for public health uses of electronic health data
Authors: McGraw Deven , Rosati Kristen , Evans Barbara
Published: January 2012

Successful implementation of a program of active safety surveillance of drugs and medical products depends on public trust. This article summarizes how the initial pilot phase of the FDA's Sentinel Initiative, Mini‐Sentinel, is being conducted in compliance with applicable federal and state laws. The article also sets forth the attributes of Mini‐Sentinel that enhance privacy and public trust, including the use of a distributed data system (where identifiable information remains at the data partners) and the adoption by participants of additional mandatory policies and procedures implementing fair information practices. The authors conclude by discussing the implications of this model for other types of secondary health data uses. Copyright © 2012 John Wiley & Sons, Ltd.
Statistical approaches to group sequential monitoring of postmarket safety surveillance data: current state of the art for use in the Mini‐Sentinel pilot
Authors: Cook Andrea J. , Tiwari Ram C. , Wellman Robert D. , Heckbert Susan R. , Li Lingling , Heagerty Patrick , Marsh Tracey , Nelson Jennifer C.
Published: January 2012

Purpose

This manuscript describes the current statistical methodology available for active postmarket surveillance of pre‐specified safety outcomes using a prospective incident user concurrent control cohort design with existing electronic healthcare data.

Methods

Motivation of the active postmarket surveillance setting is provided using the Food and Drug Administration's Mini‐Sentinel Pilot as an example. Four sequential monitoring statistical methods are presented including the Lan–Demets error spending approach, a matched likelihood ratio test statistic approach with the binomial MaxSPRT as a special case, the conditional sequential sampling procedure with stratification, and a generalized estimating equation regression approach using permutation. Information on the assumptions, limitations, and advantages of each approach is provided, including how each method defines sequential monitoring boundaries, what test statistic is used, and how robust it is to settings of rare events or frequent testing.

Results

A hypothetical example of how the approaches could be applied to data comparing a medical product of interest, drug A, to a concurrent control drug, drug B, is presented including providing the type of information one would have available for monitoring such drugs.

We have described the current state of methodology for postmarket surveillance of pre‐specified safety outcomes. We describe the limitations and advantages of the approaches while acknowledging areas for future development. Copyright © 2012 John Wiley & Sons, Ltd.
A systematic review of validated methods for identifying venous thromboembolism using administrative and claims data
Authors: Tamariz Leonardo , Harkins Thomas , Nair Vinit
Published: January 2012

Background

Venous thromboembolism (VTE) is a serious complication. Large claims databases can potentially identify the effects that medications have on VTE. The purpose of this study is to evaluate the evidence supporting the validity of VTE codes.

Methods

A search of MEDLINE database is supplemented by manual searches of bibliographies of key relevant articles. We selected all studies in which a claim code was validated against a medical record. We reported the positive predictive value (PPV) for the VTE claim compared to the medical record.

Results

Our search strategy yielded 345 studies, of which only 19 met our eligibility criteria. All of the studies reported on ICD‐9 codes, but only two studies reported on pharmacy codes, and one study reported on procedure codes. The highest PPV (65%–95%) was reported for the combined use of ICD‐9 codes 415 (pulmonary embolism), 451, and 453 (deep vein thrombosis) as a VTE event. If a specific event like DVT (PPV 24%–92%) or PE (PPV 31%–97%) was evaluated, the PPV was lower than when the combined events were examined. Studies that included patients after orthopedic surgery reported the highest PPV (96%–100%).

Conclusions

The use of ICD‐9 415, 451, and 453 are appropriate for the identification of VTE in claims databases. The codes performed best when codes were evaluated in patients at higher risk of VTE. Copyright © 2012 John Wiley & Sons, Ltd.
A Thermodynamic Model for Prediction of Iron Oxide Activity in Some FeO‐Containing Slag Systems
Authors: Yang Xue‐min , Shi Cheng‐bin , Zhang Meng , Zhang Jian
Published: January 2012

A thermodynamic model for calculating the mass action concentrations of structural units in CaO–SiO2–MgO–FeO–MnO–Al2O3–CaF2 slags, i.e., the IMCT‐Ni model, has been developed based on the ion and molecule coexistence theory (IMCT). The calculated comprehensive mass action concentration of iron oxides $N_{{\rm Fe}_{t} {\rm O}} $ has been compared with the reported activity of iron oxide $a_{{\rm Fe}_{t} {\rm O}} $ in 14 FeO‐containing slag systems from literatures. The good agreement between the calculated $N_{{\rm Fe}_{t} {\rm O}} $ and reported $a_{{\rm Fe}_{t} {\rm O}} $ indicates that the developed IMCT‐Ni model can be successfully applied to predict the activity of iron oxide $a_{{\rm Fe}_{t} {\rm O}} $ as well as the slag oxidation ability of CaO–FeO (s1), SiO2–FeO (s2), CaO–SiO2–FeO (s3), CaO–FeO–Al2O3 (s4), SiO2–MgO–FeO (s5), SiO2–FeO–Al2O3 (s6), CaO–SiO2–FeO–Al2O3 (s7), CaO–SiO2–MgO–FeO–Al2O3 (s8), SiO2–FeO–MnO (s9), SiO2–FeO–MnO–Al2O3 (s10), FeO–MnO (s11), FeO–MnO–Al2O3 (s12), CaO–FeO–CaF2 (s13), and CaO–SiO2–FeO–CaF2 slags (s14) in a temperature range of 1473–1973 K.
Comparison between transvaginal sonography, saline contrast sonovaginography and magnetic resonance imaging in the diagnosis of posterior deep infiltrating endometriosis
Authors: Saccardi C. , Cosmi E. , Borghero A. , Tregnaghi A. , Dessole S. , Litta P.
Published: January 2012

Objective

To compare clinical evaluation, transvaginal sonography (TVS), saline contrast sonovaginography (SCSV) and magnetic resonance imaging (MRI) in the diagnosis of posterior deep pelvic endometriosis (DPE).

Methods

Women suspected of having posterior DPE on the basis of subjective symptoms and clinical evaluation underwent digital vaginal and rectal examination, TVS, SCSV and MRI. Laparoscopy was performed and specimens were sent for histological examination. Sensitivity, specificity, positive and negative predictive value, as well as positive and negative likelihood ratios were analyzed for each diagnostic method.

Results

Fifty‐four out of 102 women suspected of having posterior DPE underwent laparoscopic surgery. Among these, in 46 (85.2%) cases DPE was confirmed at laparoscopic and histological examination. SCSV correctly identified 43 (93.5%) cases, presenting higher accuracy than did the other procedures. SCSV and MRI were more accurate in diagnosing and discriminating between the different locations of endometriotic lesions, with respective sensitivities of 94.7 and 73.1% for vaginal fornix, 88.9 and 66.7% for the uterosacral ligaments and 80.6 and 83.3% for involvement of the rectovaginal septum. The specificity of SCSV and MRI, respectively, was 97.1 and 94.3% for vaginal fornix, 95.6 and 95.6% for uterosacral ligaments and 100 and 77.8% for involvement of the rectovaginal septum. In the diagnosis of rectal endometriosis, we found a sensitivity of 66.7% for both techniques and specificity of 93.8% for SCSV and 95.8% for MRI.

Conclusion

TVS should be used as the first‐line diagnostic technique and SCSV and/or MRI as second‐line methods in the diagnosis of posterior DPE. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
Prognostic Factors for Recurrence of Papillary Thyroid Carcinoma in the Lymph Nodes, Lung, and Bone: Analysis of 5,768 Patients with Average 10‐year Follow‐up
Authors: Ito Yasuhiro , Kudo Takumi , Kobayashi Kaoru , Miya Akihiro , Ichihara Kiyoshi , Miyauchi Akira
Published: January 2012

Background

Papillary thyroid carcinoma (PTC) frequently recurs to the lymph nodes, which may not be fatal immediately but is a stressor for physicians and patients. Recurrence to the distant organs, although less frequent, is often life‐threatening, and the lung and bone are organs to which PTC is likely to recur. In the present study we investigated factors predicting recurrence of PTC to the lymph nodes, lung, and bone in a large number of patients undergoing long‐term follow‐up.

Methods

A total of 5,768 PTC patients (608 males and 5,159 females) without distant metastasis at diagnosis who underwent initial surgery between 1987 and 2004 in Kuma Hospital were enrolled in this study. The postoperative follow‐up ranged from 12 to 280 months, and was 129 months (10.8 years) on average.

Results

To date, node, lung, and bone recurrences have been detected in 389 (7%), 118 (2%), and 33 patients (0.6%), respectively, and 57 patients (1%) have died of PTC. We examined the prognostic significance of the tumor size (T), extrathyroid extension (Ex), age 55 years or older (Age), male gender (Gender), clinical node metastasis (N), and extranodal tumor extension (LN‐Ex) for each outcome on multivariate analysis. Age, Gender, T > 2 cm, N, and Ex were independent predictors of lymph node recurrence. Age, Ex, T > 2 cm, and N were independent prognostic factors for lung recurrence. Ex, T > 4 cm, and N independently predicted bone recurrence. Of these, N ≥ 3 cm had the strongest prognostic value for lymph node, lung, and bone recurrences. In contrast, Age was the strongest predictor for carcinoma death. LN‐Ex also had a prognostic value for carcinoma death, although it was not a predictor of carcinoma recurrence. Ex, N ≥ 3 cm, and T > 2 cm also had a prognostic impact on carcinoma death.

Conclusions

Large lymph node metastasis showed a strong prognostic impact on carcinoma recurrence not only to the lymph nodes but also to the lung and bone, and carcinoma death. Extrathyroid extension also independently predicted these recurrences and carcinoma death, although hazard ratios were lower than for large node metastasis. Age 55 years or older, in contrast, was the strongest predictor of carcinoma death. Extranodal tumor extension did not independently affect recurrence, but it had prognostic significance for carcinoma death. These findings suggest that recurring PTC lesions of older patients and/or extranodal tumor extensions are difficult to control and very progressive.
Not the Number but the Location of Lymph Nodes Matters for Recurrence Rate and Disease‐Free Survival in Patients with Differentiated Thyroid Cancer
Authors: de Meer S. G. A. , Dauwan M. , de Keizer B. , Valk G. D. , Borel Rinkes I. H. M. , Vriens M. R.
Published: January 2012

Background

Several Japanese studies have focused on identifying prognostic factors in patients with positive lymph nodes to predict recurrence rate and disease‐free survival (DFS). However, different treatment protocol is followed in Japan compared with the European and American approach. This study was designed to investigate whether the number and/or location of lymph nodes predicts prognosis in patients with DTC treated with total thyroidectomy, lymph node dissection, and postoperative radioactive iodine ablation.

Methods

All 402 patients who were treated at the Department of Nuclear Medicine between 1998 and 2010 for DTC were reviewed. Patients were treated with (near) total thyroidectomy, lymph node dissection on indication, and postoperative I‐131 ablation. Median follow‐up was 49 (range, 10–240) months. Outcome measures were recurrence rate, disease‐free survival, and mean time to recurrence.

Results

Ninety‐seven patients had proven lymph node metastases. Recurrence rate was significantly higher in patients with positive lymph nodes in the lateral compartment vs. patients with lymph node metastasis in the central compartment (60 vs. 30%, p = 0.007). Disease‐free survival and mean time to recurrence also were significantly shorter (30 vs. 52 months, p = 0.035 and 7 vs. 44 months, p = 0.004, respectively). The number of lymph nodes and extranodal growth were not significantly associated with the outcome measures used.

Conclusions

The location of positive lymph nodes was significantly correlated with the risk of recurrence and a shorter DFS. Hence, the TNM criteria are useful in subdividing patients based on risk of recurrence and DFS.
Evaluation of Postoperative Radioactive Iodine Scans in Patients who Underwent Prophylactic Central Lymph Node Dissection
Authors: Laird Amanda M. , Gauger Paul G. , Miller Barbra S. , Doherty Gerard M.
Published: January 2012

Background

Prophylactic central lymph node dissection (CLND) accompanying total thyroidectomy for papillary thyroid cancer (PTC) remains controversial. Our hypothesis is that CLND may help select patients who benefit from postoperative radioactive iodine (RAI).

Methods

A total of 119 patients who were clinically node‐negative underwent total thyroidectomy/bilateral CLND for papillary thyroid cancer (PTC) > 1 cm during 2002–2010. Pathology results, RAI results, and outcomes were compared between node‐positive (NP) and node‐negative (NN) patients.

Results

NP and NN patients were similar in age, gender, tumor size, and MACIS score. Median number of nodes excised was six. The rate of permanent hypocalcemia was 1.7% without permanent recurrent laryngeal nerve injuries. Thirteen of 52 (25%) NN patients and 24 of 67 (36%) NP patients had suspicious nodes by intraoperative inspection. The node assessment negative predictive value was 75%; positive predictive value was 36%. Fifty‐six percent (67/118) were NP; 100 patients were treated with RAI. Fourteen of 62 NP patients had abnormal postoperative RAI scans aside from the thyroid remnant versus 4 of 38 NN patients (23 vs. 11%, p = 0.18). Median 1‐year stimulated thyroglobulin (Tg) level was 0.0 for both (range 0.0–1.2, NN; 0.0–22.7, NP; p = 0.1). NP patients received higher doses of RAI (150 vs. 30 mCi, p < 0.001). Rate of recurrent or persistent disease was 3.4%.

Conclusions

Few node‐negative patients have abnormal RAI scans outside of the thyroid bed. Node‐positive patients had greater variability in stimulated 1‐year Tg levels after higher doses of RAI. CLND may identify the patients most likely to have persistently elevated stimulated Tg after initial therapy for PTC.
Jobs and Freedom Now! Functional Finance, Full Employment, and the Freedom Budget
Authors: Forstater Mathew
Published: January 2012

Forty-five years ago, the A. Philip Randolph Institute issued “The Freedom Budget,” in which a program for economic transformation was proposed that included a job guarantee for everyone ready and willing to work, a guaranteed income for those unable to work or those who should not be working, and a living wage to lift the working poor out of poverty. Such policies were supported by a host of scholars, civic leaders, and institutions, including the Rev. Dr. Martin Luther King, Jr.; indeed, they provided the cornerstones for King's “Poor Peoples’ Campaign” and “economic bill of rights.” This paper proposes a “New Freedom Budget” for full employment based on the principles of functional finance. To counter a major obstacle to such a policy program, the paper includes a “primer” on three paradigms for understanding government budget deficits and the national debt: the deficit hawk, deficit dove, and functional finance perspectives. Finally, some of the benefits of the job guarantee are outlined, including the ways in which the program may serve as a vehicle for a variety of social policies.
Racial group regard, barrier socialization, and African American adolescents’ engagement: Patterns and processes by gender
Authors: Smalls Ciara , Cooper Shauna M.
Published: January 2012

The current study examined gendered processes via 1) profiles of racial barrier socialization, regard for one’s racial group (private regard), and behavioral engagement and grades and, 2) gender and private regard as a moderator in the link between barrier messages and academic engagement outcomes. One‐hundred and twenty‐five African American adolescents (ages 10–14, M = 12.39, SD = 1.07) completed measures of socialization, private regard, grades and behavioral engagement. Latent Profile Analysis revealed a 2‐cluster solution fit the data best ‐ 1) High Engagement‐Race Salient (HERS) cluster and 2) Low Engagement‐Non‐Salient cluster (LENS). Girls had higher representation in the HERS cluster. When private regard was examined as a moderator, girls’ grades were unrelated to barrier socialization and private regard. In contrast, barrier socialization was associated with lower grades for low private regard boys. Findings are discussed in the context of gendered racial school contexts that African American youth must navigate to be academically successful.
Mild cognitive impairment: Disparity of incidence and prevalence estimates
Authors: Ward Alex , Arrighi H. Michael , Michels Shannon , Cedarbaum Jesse M.
Published: January 2012

Background

The purpose of conducting this study was to identify areas of concordance and sources of variation for the published rates of prevalence and incidence associated with various definitions for mild cognitive impairment (MCI).

Methods

The study used systematic review of studies published in English since 1984. Studies were identified by searching MEDLINE and EMBASE databases. Population‐based observational studies of incidence or prevalence of MCI and related terms were eligible for inclusion.

Results

A total of 3,705 citations were identified, and 42 were accepted for inclusion; 35 included data on prevalence and 13 on incidence. The following four terms predominated: age‐associated memory impairment (AAMI); cognitive impairment no dementia (CIND); MCI; and amnestic MCI (aMCI). Within each term, the operational definition varied. Substantial variation was observed for both incidence (MCI: 21.5–71.3; aMCI: 8.5–25.9 per 1,000 person‐years) and prevalence of each definition of cognitive impairment (AAMI 3.6%–38.4%; CIND 5.1%–35.9%; MCI 3%–42%; aMCI 0.5%–31.9%). CIND and MCI showed increasing prevalence among older age groups, whereas age‐specific rates of aMCI were lower and without any apparent age relationship.

Conclusions

Prevalence and incidence estimates associated with MCI vary greatly both between definitions and within a definition across the 42 publications. These wide differences pose a significant challenge to our understanding of the social burden of this disease. Enhancement and standardization of operational definitions of the subtypes of cognitive impairment could improve estimates of disease burden and provide a mechanism to assist in the identification of individuals at risk for future Alzheimer's disease and other dementias.
Essentiality of HIV testing and education for effective HIV control in the national pilot harm reduction program: The Taiwan experience
Authors: Lee Hsin‐Ya , Yang Yi‐Hsin , Yu Wen‐Jing , Su Lien‐Wen , Lin Tsang‐Yaw , Chiu Hsien‐Jane , Tang Hsin‐Pei , Lin Chien‐Yang , Pan Ryh‐Nan , Li Jih‐Heng
Published: January 2012

In 2005, a national pilot harm reduction program (PHRP), which mainly included a methadone maintenance treatment program (MMTP) and a needle/syringe exchange program (NSP), was implemented in Taiwan. We conducted this study to evaluate the effectiveness of harm reduction measures on HIV control among injecting drug users (IDUs) between PHRP and nonPHRP. The data on HIV, collected from incumbent Taiwanese authorities, were analyzed for their associations, risk and protective factors with PHRP measures. While the monthly HIV incidences did not show significant differences before and after PHRP in the four areas with PHRP (Taipei City, Taipei County, Taoyuan County and Tainan County), a significant increase in the HIV incidence was found in the 21 areas without PHRP. Hence, the implementation of the PHRP did result in a significant difference in the monthly HIV incidence between areas with and without the PHRP. Mandatory HIV testing was significantly associated with the HIV incidence according to the generalized estimation equations (GEE) model. With adjustments of time period and area with PHRP, and urban area, protective factors associated with HIV incidence were: educational materials, condoms, dilution water, and alcohol sponges/swabs. MMTP contributed to a higher HIV incidence, probably due to the concurrent HIV testing upon admission. Since HIV testing was not required in the NSP, the HIV testing‐dependent MMTP may explain the association of the PHRP intervention and an increased HIV incidence. In summary, HIV testing and education were essential for effective HIV control upon implementing the PHRP.
Primary small cell carcinoma of the lesser omentum
Authors: Feng Ji‐Feng , Guo Yi‐He , Chen Wen‐You , Chen Da‐Feng , Liu Jing
Published: January 2012

Although pulmonary small cell carcinoma (SCC) is seen frequently, SCC that originates from the extrapulmonary organs is extremely rare. We herein report a case of a SCC located in the lesser omentum. A 61‐year‐old male was admitted to our department due to intermittent epigastralgia for 2 months. Ultrasonography (US) revealed an irregular hypoechoic mass measuring about 58 mm × 50 mm × 45 mm under the left lobe of the liver. Magnetic resonance imaging (MRI) was performed to verify the irregular mass with T1‐ and T2‐ weighted images between the left lobe of liver and the stomach. At laparotomy, the well‐circumscribed neoplasm was found in the lesser omentum, and the fundus of the neoplasm was located in the root of left gastric artery. Intraoperative microscopic evaluation of frozen sections revealed malignancy of the lesser omentum. Resection of the neoplasm was performed, and the combined resection of the vagal nerve was also performed for the partial adhesion. Pyloroplasty was performed for avoiding delayed gastric emptying caused by combined resection of vagal nerve. The lymph nodes dissection at lesser curvature and right cardia was also performed with a negative result. Based on the histological findings, the final diagnosis of primary lesser omental SCC was confirmed. The pathologic staging showed locoregional disease.
Structural and genic characterization of stable genomic regions in breast cancer: Relevance to chemotherapy
Authors: Park Nicole I. , Rogan Peter K. , Tarnowski Heather E. , Knoll Joan H.M.
Published: January 2012

Background

Cancer genomes accumulate frequent and diverse chromosomal abnormalities as well as gene mutations but must maintain the ability to survive in vivo. We hypothesize that genetic selection acts to maintain tumour survival by preserving copy number of specific genes and genomic regions. Genomic regions and genes that remain unaltered in copy number and expression, respectively, may be essential for maintaining tumour survival.

Methods

We analyzed copy number data of 243 previously reported breast tumours and computationally derived stable copy number regions. To identify genes in stable copy number regions with nominal changes in expression, datasets for tumour and normal samples were compared. Results were replicated by analysis of a series of independent copy number, expression and genomic sequencing studies. A subset of stable regions, including stable paralogous regions, were confirmed by quantitative PCR and fluorescence in situ hybridization (FISH) in 5 breast cancer cell lines. We deduced a comprehensive set of dually stable genes (i.e. maintaining nominal copy number and expression) which were categorized according to pathway and ontology assignments. The stability of genes encoding therapeutic drug targets was also assessed.

Results and Conclusion

Tumour genome analysis revealed 766 unstable (amplified and/or deleted) and 812 stable contiguous genomic regions. Replication analysis of an independent set of 171 breast tumours confirmed copy number stability of 1.3 Gb of the genome. We found that 5804 of these genes were dually stable. The composition of this gene set remained essentially unchanged (<2% reduction) after accounting for commonly mutated breast cancer genes found by sequencing and differential expression. The stable breast cancer genome is enriched for cellular metabolism, regulation of gene expression, DNA packaging (chromatin and nucleosome assembly), and regulation of apoptosis functions. Stable genes participating in multiple essential pathways were consistently found to be targets of chemotherapies. Preservation of stable, essential genes may be related to the effectiveness of certain chemotherapeutic agents that act on multiple gene products in this set.
Prävention alkoholbezogener Störungen bei älteren Migranten. Eine cluster-randomisierte kontrollierte Studie
Authors: Bermejo Isaac , Frank Fabian , Härter Martin
Published: January 2012

Einleitung

Alkohol wird bei Migranten insbesondere ab dem 50. Lebensjahr zu einem häufigen Problem. Diese Gruppe wird aber durch alkoholbezogene Präventionsmaßnahmen nur unzulänglich erreicht. Vor diesem Hintergrund wurde am Universitätsklinikum Freiburg ein auf ältere Migranten gerichtetes transkulturelles Präventionskonzept für alkoholbezogene Störungen in einer cluster-randomisierten Studie mit n = 268 Migranten evaluiert. Akzeptanz, Bewertung und selbstangegebene Reduktion im Alkoholkonsum in der Interventionsgruppe signifikant höher. Die Berücksichtigung der Diversität bezüglich kultureller, migrationsbezogener war, soziodemographischer und sprachlicher Faktoren erhöht die Effektivität von Präventionsmaßnahmen.
Diabetesprävention: Evaluation einer evidenzbasierten Patienteninformation – randomisierte kontrollierte Studie
Authors: Genz Jutta , Haastert Burkhard , Cole Dennis , Müller Hardy , Icks Andrea
Published: January 2012

Einleitung

Evidenzbasierte Patienteninformation (EBPI), zugeschnitten auf die Bedürfnisse der Patienten, sollte als eine wichtige Basis für „informierte Entscheidungen“ in stärkerem Maße verfügbar sein (Coulter, 1998; GMC, 2008; Steckelberg et al., 2005). Die hier berichtete Studie beinhaltete die Entwicklung und Evaluation einer EBPI zu grenzwertig erhöhten Blutzuckerspiegeln und zur Primärprävention des Diabetes.
WAGED ENTREPRENEURS, POLICED INFORMALITY: WORK, THE REGULATION OF SPACE AND THE ECONOMY OF THE ZIMBABWEAN–SOUTH AFRICAN BORDER
Authors: Bolt Maxim
Published: January 2012

Keen to show the fluidity of border areas, and the limits of state control, much anthropological scholarship on borders highlights arrangements, activities and opportunities that pass beneath the official radar. But while such a clandestine focus casts border dwellers as preoccupied with resisting state regulation, this article shows how Zimbabwean–South African border dwellers make the most of their location by beingvisibleto state officials, as waged farm workers. They seek agricultural jobs as a foothold in building lucrative businesses. Moreover, waged farm workforces are hubs of border trade, as workers remit goods for resale as a response to the crisis at home in Zimbabwe. The article therefore questions the wider theoretical opposition between the creative entrepreneurship of the informal economy and the drudgery of formal employment. Formal and informal modes of livelihood constitute one another, intersect and are interdependent. This article unpacks the spatial and temporal articulations between waged work and other means of making ends meet. In so doing, it suggests fixating less on the border itself as a distinctive feature, replete with smugglers and murky goings-on, and appreciating the various meanings of work in borderland economies.
Are wider surgical margins needed for early oral tongue cancer?
Authors: Iseli T A , Lin M J , Tsui A , Guiney A , Wiesenfeld D , Iseli C E
Published: January 2012

Background:

Traditionally, a 1-cm surgical resection margin is used for early oral tongue tumours.

Methods:

All tumour stage one (n = 65) and stage two (n = 13) oral tongue cancers treated between January 1999 and January 2009 were followed for a median of 38 months (minimum 12 months). The sites of close and involved margins were histologically reviewed.

Results:

Involved and close margins occurred in 14 and 55 per cent of cases, respectively. The number of involved vs clear or close margins was equivalent in tumour stage one (90 vs 82 per cent), node-negative (100 vs 84 per cent) and perineural or lymphovascular invasion (20 vs 21 per cent) cases. Close or involved margins were similarly likely to be posterior (59 per cent) as anterior (41 per cent, p = 0.22), lateral (57 per cent) as medial (43 per cent, p = 0.34), and mucosal (59 per cent) as deep (41 per cent, p = 0.22). Local recurrence occurred in 28 per cent of cases at a median of 12 months, and was more likely in cases with involved (50 per cent) than clear or close margins (25 per cent, p = 0.10). Disease-free survival was worse in involved margins cases (p = 0.002).

Conclusion:

Involved margins are common in early tongue tumours, and are associated with increased local recurrence and worse survival. Close or involved margins occur in all directions and all tumour types. A wider margin may be justified.
Dissipation of wave energy and turbulence in a shallow coral reef lagoon
Authors: Huang Zhi‐Cheng , Lenain Luc , Melville W. Kendall , Middleton Jason H. , Reineman Benjamin , Statom Nicholas , McCabe Ryan M.
Published: January 2012

Simultaneous in situ measurements of waves, currents and turbulence are presented to describe dissipation rates of wave energy and turbulent kinetic energy in the windward coral reef‐lagoon system at Lady Elliot Island (LEI), Australia. The dissipation of wave energy in the lagoon is tidally modulated and strongly correlates with frictional dissipation due to the presence of the extremely rough bottom boundary. The observed turbulent kinetic energy (TKE) dissipation rate, ε, in this wave‐dominated lagoon is much larger than recently reported values for unidirectional flows over natural fringing coral reefs. The correlation between the wave dissipation and ε is examined. The average rate of dissipation induced by the rough turbulent flow was estimated directly from the observed ε coupled with both a depth‐integrated approach and with a bottom boundary layer scaling. Rates of TKE dissipation estimated using the two approaches approximate well, within a factor of 1.5 to 2.4, to the surface‐wave energy dissipation rate. The wave dissipation and friction factor in the lagoon can be described by a spectral wave‐frictional model with a bottom roughness length scale that is approximately constant across the lagoon. We also present estimates of dissipation induced by the canopy drag force of the coral heads. The dissipation in this case is enhanced and becomes more significant for the total energy dissipation when the water depth in the lagoon is comparable to the height of the coral heads.
Evaluation of OVATION Prime as a forecast model for visible aurorae
Authors: Machol Janet L. , Green Janet C. , Redmon Robert J. , Viereck Rodney A. , Newell Patrick T.
Published: January 2012

This study evaluates the ability of the OVATION Prime auroral precipitation model to provide operational forecasts of the visible aurora. An operational implementation would primarily provide the general public with some guidance for viewing the aurora. We evaluate the likelihood that if aurorae are predicted to be visible at a location, they will be seen there within the hour. Nighttime model forecasts were validated with Polar Ultraviolet Imager data for Kp ≥ 3 and for the years 1997 and 1998. The overall forecasts for a visible aurora to occur or to not occur were correct 77% of the time. The most important prediction for public auroral viewing is that the visible aurora will occur, and these forecasts were correct 86% of the time.
Recharge and source‐water insights from the Galapagos Islands using noble gases and stable isotopes
Authors: Warrier Rohit B. , Castro Maria Clara , Hall Chris M.
Published: January 2012

Through a combined noble gas and stable isotope study carried out in the Galapagos Islands of Santa Cruz and San Cristobal, we demonstrate the utility of atmospheric noble gases in identifying recharge areas and timing of recharge in fractured, basaltic systems. Timing of recharge obtained through noble gas temperatures (NGTs) for all samples is corroborated by stable isotopes. Except for one sample, combined NGTs and stable isotope analyses point to recharge during the hot season for all low‐altitude (<∼420 m) spring samples from San Cristobal and all basal aquifer samples in Santa Cruz. Stable isotope comparisons also indicate that San Cristobal springs located at high altitudes (>420 m above sea level) are recharged during both the “garúa” and hot seasons. Preservation of seasonality independently recorded by NGTs and stable isotopes is further reinforced by estimated young water ages. Samples located at high‐altitude display systematic deviations of dissolved noble gases from expected air saturated water values and lead to inconsistent recharge altitudes and temperatures using standard NGT models. Existing degassing models are unable to account for the observed noble gas pattern for most samples. We explore various mechanisms to assess their potential at reproducing the observed noble gas signature. In particular, the potential impact of fog droplets during the cooler “garúa” season on dissolved noble gas concentrations in groundwater and the effect of mixing high‐altitude (≥1500 m) rainwater with low‐altitude (∼400 m) fog droplets is explored. This mixing hypothesis is capable of explaining Ne and Xe concentrations for most high‐altitude samples.
Links between viruses and prokaryotes throughout the water column along a North Atlantic latitudinal transect
Authors: De Corte Daniele , Sintes Eva , Yokokawa Taichi , Reinthaler Thomas , Herndl Gerhard J
Published: January 2012

Viruses are an abundant, diverse and dynamic component of marine ecosystems and have a key role in the biogeochemical processes of the ocean by controlling prokaryotic and phytoplankton abundance and diversity. However, most of the studies on virus–prokaryote interactions in marine environments have been performed in nearshore waters. To assess potential variations in the relation between viruses and prokaryotes in different oceanographic provinces, we determined viral and prokaryotic abundance and production throughout the water column along a latitudinal transect in the North Atlantic. Depth-related trends in prokaryotic and viral abundance (both decreasing by one order of magnitude from epi- to abyssopelagic waters), and prokaryotic production (decreasing by three orders of magnitude) were observed along the latitudinal transect. The virus-to-prokaryote ratio (VPR) increased from ∼19 in epipelagic to ∼53 in the bathy- and abyssopelagic waters. Although the lytic viral production decreased significantly with depth, the lysogenic viral production did not vary with depth. In bathypelagic waters, pronounced differences in prokaryotic and viral abundance were found among different oceanic provinces with lower leucine incorporation rates and higher VPRs in the North Atlantic Gyre province than in the provinces further north and south. The percentage of lysogeny increased from subpolar regions toward the more oligotrophic lower latitudes. Based on the observed trends over this latitudinal transect, we conclude that the viral–host interactions significantly change among different oceanic provinces in response to changes in the biotic and abiotic variables.
Volumetric Dilution, Rather Than Sequestration Best Explains the Low Vitamin D Status of Obesity
Authors: Drincic Andjela T. , Armas Laura A.G. , van Diest Eileen E. , Heaney Robert P.
Published: January 2012

Vitamin D status is known to be poor in obese individuals; there is no consensus as to the reason. Cross‐sectional study of the relation between serum 25‐hydroxyvitamin D (25(OH)D) concentration and body size in the baseline data from unsupplemented adults entering two study cohorts in our research unit, N = 686. Regression analyses of body size variables against serum 25(OH)D concentration, using both linear and hyperbolic models. The fit to a hyperbolic model of 25(OH)D against body weight completely removed the obesity‐related component of inter‐individual variability in serum 25(OH)D concentration. The hyperbolic fit using total body weight was significantly better than any linear model, and specifically better than any using BMI. Dilution of ingested or cutaneously synthesized vitamin D in the large fat mass of obese patients fully explains their typically low vitamin D status. There is no evidence for sequestration of supplemental or endogenous cholecalciferol. Vitamin D replacement therapy needs to be adjusted for body size if desired serum 25(OH)D concentrations are to be achieved.
Biochemical identification of the OsMKK6–OsMPK3 signalling pathway for chilling stress tolerance in rice
Authors: Xie Guosheng , Kato Hideki , Imai Ryozo
Published: January 2012

MAPK (mitogen-activated protein kinase) pathways have been implicated in stress signalling in plants. In the present study, we performed yeast two-hybrid screening to identify partner MAPKs for OsMKK (Oryza sativa MAPK kinase) 6, a rice MAPK kinase, and revealed specific interactions of OsMKK6 with OsMPK3 and OsMPK6. OsMPK3 and OsMPK6 each co-immunoprecipitated OsMKK6, and both were directly phosphorylated by OsMKK6 in vitro. An MBP (myelin basic protein) kinase assay of the immunoprecipitation complex indicated that OsMPK3 and OsMPK6 were activated in response to a moderately low temperature (12°C), but not a severely low temperature (4°C) in rice seedlings. A constitutively active form of OsMKK6, OsMKK6DD, showed elevated phosphorylation activity against OsMPK3 and OsMPK6 in vitro. OsMPK3, but not OsMPK6, was constitutively activated in transgenic plants overexpressing OsMKK6DD, indicating that OsMPK3 is an in vivo target of OsMKK6. Enhanced chilling tolerance was observed in the transgenic plants overexpressing OsMKK6DD. Taken together, our data suggest that OsMKK6 and OsMPK3 constitute a moderately low-temperature signalling pathway and regulate cold stress tolerance in rice.
Sphingosine 1-phosphate signalling in cancer
Authors: Pyne Nigel J. , Tonelli Francesca , Lim Keng Gat , Long Jaclyn S. , Edwards Joanne , Pyne Susan
Published: January 2012

There is an increasing body of evidence demonstrating a critical role for the bioactive lipid S1P (sphingosine 1-phosphate) in cancer. S1P is synthesized and metabolized by a number of enzymes, including sphingosine kinase, S1P lyase and S1P phosphatases. S1P binds to cell-surface G-protein-coupled receptors (S1P1–S1P5) to elicit cell responses and can also regulate, by direct binding, a number of intracellular targets such as HDAC (histone deacetylase) 1/2 to induce epigenetic regulation. S1P is involved in cancer progression including cell transformation/oncogenesis, cell survival/apoptosis, cell migration/metastasis and tumour microenvironment neovascularization. In the present paper, we describe our research findings regarding the correlation of sphingosine kinase 1 and S1P receptor expression in tumours with clinical outcome and we define some of the molecular mechanisms underlying the involvement of sphingosine kinase 1 and S1P receptors in the formation of a cancer cell migratory phenotype. The role of sphingosine kinase 1 in the acquisition of chemotherapeutic resistance and the interaction of S1P receptors with oncogenes such as HER2 is also reviewed. We also discuss novel aspects of the use of small-molecule inhibitors of sphingosine kinase 1 in terms of allosterism, ubiquitin–proteasomal degradation of sphingosine kinase 1 and anticancer activity. Finally, we describe how S1P receptor-modulating agents abrogate S1P receptor–receptor tyrosine kinase interactions, with potential to inhibit growth-factor-dependent cancer progression.
Controlling cancer through the autotaxin–lysophosphatidic acid receptor axis
Authors: Gotoh Mari , Fujiwara Yuko , Yue Junming , Liu Jianxiong , Lee SueChin , Fells James , Uchiyama Ayako , Murakami-Murofushi Kimiko , Kennel Stephen , Wall Jonathan , Patil Renukadevi , Gupte Renuka , Balazs Louisa , Miller Duane D. , Tigyi Gabor J.
Published: January 2012

LPA (lysophosphatidic acid, 1-acyl-2-hydroxy-sn-glycero-3-phosphate), is a growth factor-like lipid mediator that regulates many cellular functions, many of which are unique to malignantly transformed cells. The simple chemical structure of LPA and its profound effects in cancer cells has attracted the attention of the cancer therapeutics field and drives the development of therapeutics based on the LPA scaffold. In biological fluids, LPA is generated by ATX (autotaxin), a lysophospholipase D that cleaves the choline/serine headgroup from lysophosphatidylcholine and lysophosphatidylserine to generate LPA. In the present article, we review some of the key findings that make the ATX–LPA signalling axis an emerging target for cancer therapy.
Cross-talk between mitogenic Ras/MAPK and survival PI3K/Akt pathways: a fine balance
Authors: Aksamitiene Edita , Kiyatkin Anatoly , Kholodenko Boris N.
Published: January 2012

In the present paper, we describe multiple levels of cross-talk between the PI3K (phosphoinositide 3-kinase)/Akt and Ras/MAPK (mitogen-activated protein kinase) signalling pathways. Experimental data and computer simulations demonstrate that cross-talk is context-dependent and that both pathways can activate or inhibit each other. Positive influence of the PI3K pathway on the MAPK pathway is most effective at sufficiently low doses of growth factors, whereas negative influence of the MAPK pathway on the PI3K pathway is mostly pronounced at high doses of growth factors. Pathway cross-talk endows a cell with emerging capabilities for processing and decoding signals from multiple receptors activated by different combinations of extracellular cues.
cAMP-dependent allostery and dynamics in Epac: an NMR view
Authors: Selvaratnam Rajeevan , Akimoto Madoka , VanSchouwen Bryan , Melacini Giuseppe
Published: January 2012

Epac (exchange protein directly activated by cAMP) is a critical cAMP receptor, which senses cAMP and couples the cAMP signal to the catalysis of guanine exchange in the Rap substrate. In the present paper, we review the NMR studies that we have undertaken on the CBD (cyclic-nucleotide-binding domain) of Epac1. Our NMR investigations have shown that cAMP controls distal autoinhibitory interactions through long-range modulations in dynamics. Such dynamically mediated allosteric effects contribute not only to the cAMP-dependent activation of Epac, but also to the selectivity of Epac for cAMP in contrast with cGMP. In addition, we have mapped the interaction networks that couple the cAMP-binding site to the sites involved in the autoinhibitory interactions, using a method based on the covariance analysis of NMR chemical shifts. We anticipate that this approach is generally applicable to dissect allosteric networks in signalling domains.